Glucagon receptor family: Introduction

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing. » Email us

General

Glucagon, glucagon-like peptide 1 (GLP-1), and glucagon-like peptide 2 (GLP-2) are peptide hormones encoded by a single common prohormone precursor, proglucagon [6,63]. The sequence of 29 amino acid (aa) pancreatic glucagon is highly conserved in mammals. Glucagon is synthesised mainly in islet A cells and the brain and has also been localised to specific cells in the stomach and intestine in some species [62]. Further processing of glucagon may also produce the C-terminal undecapeptide miniglucagon, a powerful inhibitor of insulin secretion [23].

Glucagon

Glucagon regulates blood glucose via control of hepatic glycogenolysis and gluconeogenesis [95] and via regulation of insulin release from the β cell [69,111]. Pharmacological administration of glucagon increases blood glucose in normal and diabetic subjects [99], and produces positive inotropic and chronotropic cardiovascular effects [144], relaxation of smooth muscle in the gastrointestinal tract and stimulation of growth hormone secretion [91].

The actions of glucagon are mediated via a single adenylate cyclase-coupled glucagon receptor [104] that also couples to the phospholipase C-inositol phosphate (PLC--IP) pathway leading to Ca2+ release from intracellular stores [142]. Cloning of the glucagon receptor cDNAs [68,125] identified a seven-transmembrane domain (7TM) receptor localised to human chromosome 17q25 [78]. The rat and mouse glucagon receptors are 485aa, 7TM proteins with four N-linked glycosylation sites and a RLAR sequence in the third intracellular loop, a motif known to be required for G protein activation [13,68,78,125]. The human receptor cDNA encodes a 477aa receptor that contains a similar (RLAK) G protein-coupling motif as well as four N-linked glycosylation sites [13,78,81].

Glucagon-like peptide-1

Peptidergic signals derived from the intestine augment the insulin response induced by nutrients (the 'incretin effect') [32]. This functional connection between intestine and the islets of Langerhans was termed the 'incretin axis' or 'entero-insular-axis' [32]. The gut-derived GLP-1 is an important mediator in this axis [26].

Glucagon-like peptide 1 is a major end-product of the post-translational processing of proglucagon in the intestinal L-cells. At the pancreatic β-cells it stimulates insulin release via specific receptors in a glucose-dependent manner. In addition to its potent insulinotropic action, GLP-I suppresses glucagon secretion from the islet α-cells, and increases proinsulin gene transcription and insulin production [26]. Glucagon-like peptide 1 has CNS effects resulting in delayed gastric emptying [115] and appetite regulation [57,134].

Glucagon-like peptide 1 receptors were initially identified on rat insulinoma-derived cells [29,39] and, subsequently, in other insulinoma cells [32] as well as on rat [93] and human pancreatic islet cells, somatostatin-secreting cells [33,54], isolated rat parietal cells [116,135], human gastric cancer cells (HGT-1) [59], solubilised membranes of rat epididymal adipose tissue [137], 3T3-L1 adipocytes [94], membranes from the rodent thyrotrope cell line α-TSH [4], and in rat lung [106-107] and brain [44,118,136,143].

Analysis of data obtained from binding experiments with RINm5F cells revealed that GLP-1 binds to a single class of binding sites [39]. Cross-linking studies with 125[I]-GLP-1 demonstrate a single band with an apparent molecular mass of 63,000 [40,42]. The GLP-1 receptor protein is glycosylated and this is important for its function [43].

Molecular characterization of the GLP-1 receptor was achieved by cloning the rat and human β-cell GLP-1 receptor cDNAs [25,53,128-129,138] followed by isolation of cDNAs encoding the rat lung and the brain GLP-1 receptor [25,40,42-43,53,72,128-129,138,143]. The receptor protein consists of 463aa. At the amino acid level, rat and human GLP-1 receptors exhibit 90% sequence identity. The amino acid sequence contains a large hydrophilic, extracellular domain preceded by a short leader sequence required for receptor translocation across the endoplasmic reticulum during biosynthesis, and seven hydrophobic, membrane spanning domains that are linked by hydrophilic intra- and extracellular loops [130].

The human GLP-1 receptor gene has been localised to the long arm of chromosome 6 [123]. The GLP-1 receptor gene spans 40kb and consists of at least seven exons. The 5' flanking (promoter) region of the human GLP-1 receptor gene has been cloned and functionally characterized [73]. The cell- and tissue-specific expression of the GLP-1 receptor is mainly achieved by silencing cis-regulatory elements located between -574 and -2921 [45,146].

Studies investigating the distribution of rat and human GLP-1 receptor mRNA by sensitive methods such as RNAse protection assay and RT-PCR, detected GLP-1 receptor mRNA transcripts in pancreatic islets, lung, brain, stomach, heart and kidney but not in liver, skeletal muscle or adipose tissue of most species [11,25,40,42-43,45,53,72-73,123,128-130,138,143,146].

The GLP-1 receptor is functionally coupled to adenylate cyclase via a stimulatory G protein. Glucagon-like peptide 1-binding at pancreatic β-cells increases free cytosolic Ca2+ concentrations after cell depolarization [41,65-66,79,147]. Glucagon-like peptide 1 may enhance cytosolic Ca2+ independently of protein kinase A [8].

Homologous desensitization and internalization of the GLP-1 receptor are strictly dependent on the phosphorylation of three serine doublets within the cytoplasmatic tail [145]. Experiments with mutant GLP-1 receptors reveal that the number of phosphorylation sites correlates with the extent of desensitization and internalization. However, the two processes showed a different quantitative impairment in single and double mutants suggesting control by different molecular mechanisms [145].

For a recent review on review the current understanding of the structures of GLP-1 and GLP-1R, the molecular basis of their interaction, and the signaling events associated with it, see de Graaf et al., 2016 [52].

Glucagon-like peptide 2

Glucagon-like peptide 2 was first identified as a novel peptide encoded within the mammalian proglucagon cDNA sequence 3' of the sequence encoding to GLP-1 [5-6]. The GLP-2 amino acid sequence is flanked by pairs of dibasic residues characteristic of prohormone cleavage sites. Glucagon-like peptide 2 is co-secreted along with GLP-1 and glicentin from intestinal endocrine cells. The principal role of GLP-2 appears to be the maintenance of growth and absorptive function of the intestinal mucosal villus epithelium [27]. Glucagon-like peptide 2 administration to rodents enhances villus growth and increases small bowel mass, with weaker but detectable trophic effects observed in the large bowel and stomach [28,131-132]. Glucagon-like peptide 2 also upregulates hexose transport and nutrient absorption [10,19] and enhances sugar absorption and intestinal adaptation in rats with major small bowel resection [117]. Although GLP-2 binding sites have not yet been reported on cell lines and tissues, a GLP-2 receptor was isolated from hypothalamic and intestinal cDNA libraries using a combined PCR-expression cloning approach [97]. Consistent with the finding that GLP-2 stimulates adenylate cyclase activity in hypothalamic and pituitary membranes [97], GLP-2 increases intracellular cAMP in fibroblasts transfected with the rat or human GLP-2 receptor cDNA [97,149]. The GLP-2 receptor appears highly specific for GLP-2, and is expressed predominantly in the gastrointestinal tract and CNS.

Gastric inhibitory polypeptide

Gastric inhibitory polypeptide (GIP), also known as glucose-dependent inhibitory polypeptide is synthesised in and secreted from enteroendocrine K-cells in the duodenum and jejunum. Although originally identified as an inhibitor of gastric acid secretion, the best known action of GIP is the potentiation of glucose-dependent insulin secretion via GIP receptors expressed on islet β-cells. Evidence from studies using GIP receptor antagonists and GIP receptor -/- mice demonstrates the physiological importance of GIP action for the normal cell secretory response to glucose [92,133]. The actions of GIP are modulated by the physiological degradation of the peptide via N-terminal cleavage by the aminopeptidase dipeptidyl peptidase IV [70].

Secretin

The term 'hormone' was introduced by Bayliss and Starling almost one hundred years ago in response to the observation that a compound extracted from the duodenum could stimulate pancreatic fluid secretion [3]. This secretin molecule was subsequently purified and identified as a linear 27-residue peptide [98]. While species differences in this hormone have subsequently been found, with minimal differences in bovine, canine, rat, and human forms and substantial differences in chicken secretin, molecular variants or alternate forms have not yet been reported in any single species [16-17,51,101,119]. Secretin is produced and secreted by scattered single endocrine cells within the proximal intestinal mucosa (S-cells) in response to luminal acid and fatty acids [113]. Well-established, physiologically relevant targets for this hormone include the ductular epithelial cells in the pancreas and biliary tree, where secretin stimulates alkaline secretion to neutralise the luminal acid and thereby protect the intestinal mucosa [148]. In addition, stimulation of both pepsinogen and Brunner's gland secretion, and slowing of gastric emptying and intestinal transit all contribute to an optimal intraluminal milieu for digestion [12]. All these actions are currently explained by the activity of a single molecular form of secretin on a single form of the secretin receptor. Central nervous system and cardiac effects of this hormone have also been described. Unfortunately, an adequately selective small molecule, orally active secretin receptor agonist or antagonist has not yet been described.

Growth hormone-releasing hormone

Growth hormone-releasing hormone (GHRH) was initially isolated from pancreatic tumours that caused acromegaly [56,108], and later characterized from the hypothalamus [77,120] based on its ability to stimulate growth hormone secretion from primary cultures of rat pituitary cells. Growth hormone-releasing hormone is released from neurosecretory cells in the arcuate nuclei of the hypothalamus [89,112], and along with the inhibitory peptide, somatostatin, mediates the neuroendocrine regulation of pituitary growth hormone synthesis and secretion. GHRH is also expressed in the placenta, where it may have paracrine functions or contribute to foetal growth [82,124]; in the gonads, where it may be an autocrine or paracrine regulator of steroidogenesis and granulosa or Sertoli cell function [1,7,21]; and in lymphocytes, where it may modulate lymphocyte activation and immune function [122]. An important role for GHRH in post-embryonic growth is suggested by clinical studies with tumours that secrete GHRH [36-37], and by animal studies using transgenic mice that overexpress GHRH [58,121]. In these examples of GHRH excess, growth hormone hypersecretion, pituitary somatotroph cell hyperplasia and inappropriate patterns of growth (acromegaly or gigantism) are observed.

Growth hormone-releasing hormone is a peptide hormone of 42-44aa (depending on the species) that is proteolytically processed from a larger precursor protein of 103-108aa [38,86,124]. The GHRH precursor also encodes an additional C-terminal peptide that is reported to modulate Sertoli cell activity in the testis [9]. GHRH is structurally related to a large family of peptide hormones including secretin, glucagon, GLP-1 and GLP-2, vasoactive intestinal peptide, pituitary adenylate cyclase-activating polypeptide, peptides with histidine as N-terminus and isoleucine as C-terminus, and GIP [14].

The mature peptide is amidated at the C-terminus in many species, but not in rodents. Shorter processed forms of the full-length human peptide GHRH(1-44)NH2 have been characterized, with the predominant forms being GHRH(1-40)OH in hypothalamus [77] and GHRH(1-37)NH2 in a pancreatic tumour [56,108]. Carboxyl-terminally truncated peptides as short as GHRH(1-29)NH2 display growth hormone-releasing activity comparable to that of the full-length peptide [1,7,9,14,21,36-38,55,58,76-77,82,85-86,89,112,120-122,124], and GHRH(1-29)NH2 has therefore served as the template for the design of most GHRH receptor agonists and antagonists.

Several modifications to GHRH, including substitution of the conserved alanine at position 2 with other residues such as D-alanine, improve in vivo potency [71], largely by inhibition of proteolytic degradation by dipeptidylpeptidase IV, which rapidly hydrolyses the Ala2-Asp3 bond and inactivates GHRH in serum [35]. Enhancement of the amphipathic α-helical properties of GHRH by alanine replacement results in enhanced receptor affinity and increased potency in in vitro assays [18,22], and an analogue with 48% alanine content, [D-Ala2, Ala8,9,15,16,18,22,24-28]GHRH(1-29)NH2 (NC-9-45) is 1.9-fold more potent than the parent compound [22]. Analogues combining the degradation stabilising replacements at position 2 with α-helix-enhancing modifications such as the Ala15 substitution have been particularly effective for increasing activity in vitro and in vivo [142].

Replacement of the conserved alanine at position 2 of GHRH with D-arginine converts the hormone into a competitive antagonist [109]. Working with this compound, a subsequent generation of potent GHRH antagonists were developed (the MZ series) containing the helix-stabilising substitutions Phe(4-Cl) at position 6, α-aminobutyric acid at position 15 and norleucine at position 27, together with a hydrophobic N-terminal acyl moiety and a C-terminal agmatine [150]. Representative examples include MZ-4-71 and MZ-5-156. The more recent series of antagonists, the JV series, incorporate arginine or homoarginine at position 9 and an enzymatically resistant C-terminal D-Arg28-Har29-NH2 group [139]. Representative examples include JV-1-36 and JV-1-38. These antagonists are being developed largely as potential antitumour agents, in that they inhibit the growth of many tumour cells, probably by suppression of IGF-1 or IGF-2 production [114].

The GHRH receptor was initially cloned from human, rat and mouse pituitary, and in these species the isolated cDNAs encode a 423aa protein [47,74,84]. The porcine receptor was later identified as a 451aa protein, but it appears that there are several isoforms with differing C-termini, presumably generated by alternative RNA processing [67]. The predicted GHRH receptor protein has the seven potential membrane-spanning motifs of a G protein-coupled receptor, it is homologous to the receptors for peptides related to GHRH, it has the molecular size expected from GHRH photoaffinity cross-linking studies, and it is expressed predominantly in the anterior pituitary gland, the site of GHRH action [46,88].

When the GHRH receptor protein is expressed in transfected cells, these cells acquire the ability to bind GHRH with high affinity and selectivity and to respond to GHRH to activate adenylate cyclase and increase intracellular levels of the second messenger cAMP [24,47,61,84]. In somatotroph cells, GHRH also stimulates an influx of Ca2+ [64,80] most likely through voltage-sensitive Ca2+ channels [20]. While GHRH is reported to stimulate the PLC-IP pathway in pituitary cells in some studies [15,102], other studies report no activation of this pathway [31,34], and no coupling of the cloned receptor to this signalling pathway has yet been detected in transfected cells [90]. A recent study suggests that distinct somatotroph cell subpopulations may respond differently to GHRH with respect to activation of the phospholipid turnover signalling pathway [105].

Although the predominant site of GHRH receptor expression is the pituitary gland, the receptor mRNA has been localized to numerous other tissues, including the placenta, a site of GHRH production [87], the kidney [83,87], and the hypothalamus [126]. Using sensitive RT-PCR-Southern blotting assays, the receptor transcript has been found in an extremely wide range of rat tissues [83], although expression of the protein has not yet been demonstrated and the physiological significance of this broad expression remains unclear. Within the pituitary gland, expression is confined to the anterior lobe [74,84]. It remains uncertain whether pituitary cells other than the growth hormone-secreting somatotrophs express the GHRH receptor.

The GHRH receptor gene maps to the centromeric region of mouse chromosome 6 [50,75], and to human chromosome 7p14/15 [49,140]. The gene has been characterized in detail in the human [103], mouse [75] and rat [90], and consists of 13 major exons spanning approximately 15kb of DNA. The rat gene includes 14 exons, and exon 11 is included in an alternatively spliced variant mRNA, resulting in the insertion of 41aa into the third intracellular domain of the receptor. This variant receptor binds GHRH, but does not mediate signalling through the cAMP pathway [90]. An alternatively spliced form of the human GHRH receptor that is truncated following the fifth transmembrane domain has been identified both in normal pituitary and in pituitary adenomas [60,127], and is reported to exert a dominant inhibitory effect on signalling by the normal receptor in co-transfection experiments [96]. Alternative RNA processing probably contributes to the C-terminal heterogeneity observed for the porcine GHRH receptor [67], and for the dwarf rat GHRH receptor [151].

An inactivating mutation of the GHRH receptor was first reported in the little mouse [50,75]. This is an autosomal recessive mutation mapping to chromosome 6 that results in somatotroph hyperplasia, growth hormone deficiency, and a dwarf phenotype in the homozygous mutant animals [30]. There is a missense mutation in the GHRH receptor gene of the little mouse, resulting in replacement of the aspartic acid at position 60 in the N-terminal extracellular domain of the receptor with glycine [50,75]. This mutation does not affect the expression or cellular localisation of the mutant receptor protein, but it abolishes binding of GHRH by the mutant receptor, resulting in a loss of GHRH signalling and subsequent defects in somatotroph proliferation and function [48]. Several mutations leading to inactivation of the GHRH receptor have been reported in humans. Three distinct kindreds from India [141], Pakistan [2] and Sri Lanka [100] have been reported that have a nonsense mutation truncating the GHRH receptor at position 72 in the N-terminal extracellular domain. A Brazilian kindred has a mutation in a splice donor site that leads to retention of the first intron, a shift in the translational reading frame, and truncation of the receptor protein at position 20, near the probable signal sequence cleavage site [110].

References

Show »

1. Bagnato A, Catt KJ. (1992) Expression of the growth hormone-releasing hormone gene and its peptide product in the rat ovary. Endocrinology130: 1097-1102. [PMID:1537276]

2. Baumann G, Maheshwari H. (1997) The Dwarfs of Sindh: severe growth hormone (GH) deficiency caused by a mutation in the GH-releasing hormone receptor gene. Acta Paediatr. Suppl.423: 33-38. [PMID:9401536]

3. Bayliss WM, Starling EH. (1902) On the causation of the so-called 'peripheral reflex secretion' of the pancreas. Proc. R. Soc. Lond. B Biol. Sci.69: 352-353.

4. Beak SA, Smith DM. (1996) Glucagon-like peptide-1 (GLP-1) releases thyrotropin (TSH): characterization of binding sites for GLP-1 onα-TSH cells. Endocrinology137: 4130-4138. [PMID:8828468]

5. Bell GI, Najarian RC. (1983) Exon duplication and divergence in the human preproglucagon gene. Nature304: 368-371. [PMID:6877358]

6. Bell GI, Santerre RF, Mullenbach GT. (1983) Hamster preproglucagon contains the sequence of glucagon and two related peptides. Nature302: 716-718. [PMID:6835407]

7. Berry SA, Pescovitz OH. (1988) Identification of a rat GHRH-like substance and its messenger RNA in rat testis. Endocrinology123: 661-663. [PMID:3133203]

8. Bode HP, Moormann B, Dabew R, Göke B. (1999) Glucagon-like peptide 1 elevates cytosolic calcium in pancreatic β-cells independently of protein kinase A. Endocrinology140: 3919-3927. [PMID:10465260]

9. Breyer PR, Pescovitz OH. (1996) A novel peptide from the growth hormone releasing hormone gene stimulates Sertoli cell activity. Endocrinology137: 2159-2162. [PMID:8612561]

10. Brubaker PL, Drucker DJ. (1997) Intestinal function in mice with small bowel growth induced by glucagon-like peptide-2. Am. J. Physiol.272: E1050-E1058. [PMID:9227451]

11. Bullock BP, Habener JF. (1996) Tissue distribution of messenger ribonucleic acid encoding the rat glucagon-like peptide 1 receptor. Endocrinology137: 2968-2978. [PMID:8770921]

12. Bunnett NW. (1994) Gastrin-releasing peptide. in Gut Peptides Edited by Walsh JH, Dockray GJ Raven Press. 423-445 [ISBN:0781701155]

13. Burcelin R, Charron MJ. (1995) Cloning and sequence analysis of the murine glucagon receptor-encoding gene. Gene164: 305-310. [PMID:7590348]

14. Campbell RM, Scanes CG. (1992) Evolution of the growth hormone-releasing factor (GRF) family of peptides. Growth Regul.2: 175-191. [PMID:1290954]

15. Canonico PL, MacLeod RM. (1983) Human pancreatic GRF stimulates phosphatidylinositol labeling in cultured anterior pituitary cells. Am. J. Physiol.245: E587-E590. [PMID:6140852]

16. Carlquist M, Johansson C. (1985) Human secretin is not identical to the porcine/bovine hormone. IRCS Med. Sci.13: 217-218.

17. Carlquist M, Mutt V. (1981) Isolationand amino acid sequence of bovine secretin. FEBS Lett.127: 71-74. [PMID:7250377]

18. Cervini LA, Rivier JE. (1998) Human growth hormone-releasing hormone hGHRH(1-29)-NH2: systematic structure-activity relationship studies. J. Med. Chem.41: 717-727. [PMID:9513600]

19. Cheeseman CI, Tsang R. (1996) The effect of gastric inhibitory polypeptide and glucagon like peptides on intestinal hexose transport. Am. J. Physiol. Gastrointest. Liver Physiol.271: G477-G482. [PMID:8843773]

20. Chen C, Clarke IJ. (1994) Ion channels and the signal transduction pathways in the regulation of growth hormone secretion. Trends Endocrinol. Metab.5: 227-233. [PMID:18407212]

21. Ciampani T, Dufau ML. (1992) Growth hormone-releasing hormone is produced by rat Leydig cell in culture and acts as a positive regulator of Leydig cell function. Endocrinology131: 2785-2792. [PMID:1332849]

22. Coy DH, Murphy WA. (1996) Structural simplification of potent growth hormone-releasing hormone analogs: implications for other members of the VIP/GHRH/PACAP family. Ann. N.Y. Acad. Sci.805: 149-158. [PMID:8993400]

23. Dalle S, Smith P, Blache P, Le-Nguyen D, Le Brigand L, Bergeron F, Ashcroft FM, Bataille D. (1999) Miniglucagon (glucagon 19-29), a potent and efficient inhibitor of secretagogue-induced insulin release through a Ca2+ pathway. J. Biol. Chem.274 (16): 10869-76. [PMID:10196164]

24. DeAlmeida VI, Mayo KE. (1998) Identification of binding domains of the growth hormone-releasing hormone receptor by analysis of mutant and chimeric receptor proteins. Mol. Endocrinol.12: 750-765. [PMID:9605937]

25. Dillon JS, Boyd AE. (1993) Cloning and functional expression of the human glucagon-like peptide-1 (GLP-1) receptor. Endocrinology133: 1907-1910. [PMID:8391428]

26. Drucker DJ. (1998) The glucagon-like peptides. Diabetes47: 159-169. [PMID:9519708]

27. Drucker DJ, Brubaker PL. (1996) Induction of intestinal epithelial proliferation by glucagon-like peptide 2. Proc. Natl. Acad. Sci. U.S.A.93: 7911-7916. [PMID:8755576]

28. Drucker DJ, Brubaker PL. (1997) Intestinal response to growth factors administered alone or in combination with h[Gly2]-Glucagon-like peptide 2. Am. J. Physiol.273: G1252-G2262. [PMID:9435550]

29. Drucker DJ, Habener JF. (1987) Glucagon-like peptide I stimulates insulin gene expression and increases cyclic AMP levels in a rat islet cell line. Proc. Natl. Acad. Sci. U.S.A.84: 3434-3438. [PMID:3033647]

30. Eicher EM, Beamer WG. (1976) Inherited ateliotic dwarfism in mice. Characteristics of the mutation, little, on chromosome 6. J. Hered.67: 87-91. [PMID:1270792]

31. Escobar DC, Cocchi D. (1986) Growth hormone-releasing factor does not stimulate phosphoinositides breakdown in primary cultures of rat and human pituitary cells. Acta Endocrinol. (Copenh.)112: 345-350. [PMID:3019052]

32. Fehmann H-C, Goke B. (1995) Cell and molecular biology of the incretin hormones glucagon-like peptide 1 and glucose-dependent releasing polypeptide. Endocr. Rev.16: 390-410. [PMID:7671853]

33. Fehmann HC, Habener JF. (1991) Functional receptors for the insulinotropic hormone glucagon-like peptide-I(737) on a somatostatin secreting cell line. FEBS Lett.279: 335-340. [PMID:1672112]

34. French MB, Kraicer J. (1990) Effect of growth hormone-releasing factor on phosphoinositide hydrolysis in somatotrophs. Mol. Cell. Endocrinol.72: 221-226. [PMID:1963157]

35. Frohman LA, Felix AM. (1989) Dipeptidyl peptidase IV and trypsin-like enzymatic degradation of human growth hormone-releasing hormone in plasma. J. Clin. Invest.83: 1533-1540. [PMID:2565342]

36. Frohman LA, Jansson JO. (1986) Growth hormone-releasing hormone. Endocr. Rev.7: 223-253. [PMID:2874984]

37. Frohman LA, Szabo M. (1981) Ectopic production of growth hormone-releasing factor by carcinoid and pancreatic islet tumors associated with acromegaly. Prog. Clin. Biol. Res.74: 259-271. [PMID:6275403]

38. Frohman MA, Frohman LA. (1989) Cloning and characterization of mouse growth hormone-releasing hormone (GRH) complementary DNA: increased GRH messenger RNA levels in the growth hormone-deficient lit/lit mouse. Mol. Endocrinol.3: 1529-1536. [PMID:2481813]

39. Göke R, Conlon JM. (1988) Receptors for glucagon-like peptide-1(736) amide on rat insulinoma-derived cells. J. Endocrinol.116: 357-362. [PMID:2832504]

40. Göke R, Conlon JM. (1989) Characterization of the receptor for glucagon-like peptide-1(7-36) amide on plasma membranes from rat insulinoma-derived cells by covalent cross-linking. J. Mol. Endocrinol.2: 93-98. [PMID:2550026]

41. Göke R, Göke B. (1989) Signal transmission after GLP-1(7-36)amide binding in RINm5F cells. Am. J. Physiol.257: G397-G401. [PMID:2469115]

42. Göke R, Göke B. (1992) Solubilization of active GLP-1 (7-36) amide receptors from RINm5F plasma membranes. FEBS Lett.300: 232-236. [PMID:1313374]

43. Göke R, Göke B. (1994) Glycosylation of the GLP-1 receptor is a prerequisite for regular receptor function. Peptides15: 675-681. [PMID:7937345]

44. Göke R, Sheikh SP. (1995) Identification of specific binding sites for glucagon-like peptide-1 on the posterior lobe of the rat pituitary. Neuroendocrinology62: 130-134. [PMID:8584112]

45. Galehshahi FS, Lankat-Buttgereit B. (1998) Contribution of a PS1-like element to the tissue- and cell-specific expression of the human GLP-1 receptor gene. FEBS Lett.436: 163-168. [PMID:9781671]

46. Gaylinn BD. (1999) Molecular and cell biology of the growth hormone-releasing hormone receptor. Growth Horm. IGF Res.9: 37-44. [PMID:10429879]

47. Gaylinn BD, Thorner MO. (1993) Molecular cloning and expression of a human anterior pituitary receptor for growth hormone-releasing hormone. Mol. Endocrinol.7: 77-84. [PMID:7680413]

48. Gaylinn BD, Thorner MO. (1999) The mutant growth hormone-releasing hormone (GHRH) receptor of the little mouse does not bind GHRH. Endocrinology140: 5066-5074. [PMID:10537133]

49. Gaylinn BD, von Kap-Herr C, Golden WL, Thorner MO. (1994) Assignment of the human growth hormone-releasing hormone receptor gene (GHRHR) to 7p14 by in situ hybridization. Genomics19: 193-195. [PMID:8188233]

50. Godfrey P, Mayo KE. (1993) GHRH receptor of little mice contains a missense mutation in the extracellular domain that disrupts receptor function. Nat. Genet.4: 227-232. [PMID:8395283]

51. Gossen D, Christophe J. (1989) Isolation and primary structure of rat secretin. Biochem. Biophys. Res. Commun.160: 862-867. [PMID:2719704]

52. Graaf Cd, Donnelly D, Wootten D, Lau J, Sexton PM, Miller LJ, Ahn JM, Liao J, Fletcher MM, Yang D et al.. (2016) Glucagon-Like Peptide-1 and Its Class B G Protein-Coupled Receptors: A Long March to Therapeutic Successes. Pharmacol. Rev.68 (4): 954-1013. [PMID:27630114]

53. Graziano MP, Strader CD. (1993) Cloning and functional expression of a human glucagon-like peptide-1 receptor. Biochem. Biophys. Res. Commun.196: 141-146. [PMID:8216285]

54. Gros L, Demiprence E, Bataille D, Kervra A. (1992) Characterization of high affinity receptors for glucagon-like peptide-1 (7-36) amide on a somatostatin-secreting cell line. Biomed. Res.13: 143-150.

55. Gubler U, Monahan JJ, Lomedico PT, Bhatt RS, Collier KJ, Hoffman BJ, Böhlen P, Esch F, Ling N, Zeytin F et al.. (1983) Cloning and sequence analysis of cDNA for the precursor of human growth hormone-releasing factor, somatocrinin. Proc. Natl. Acad. Sci. U.S.A.80 (14): 4311-4. [PMID:6192430]

56. Guillemin R, Wehrenberg WB. (1982) Growth hormone-releasing factor from a human pancreatic tumor that caused acromegaly. Science218: 585-587. [PMID:6812220]

57. Gutzwiller JP, Beglinger C. (1999) Glucagon-like peptide-1 promotes satiety and reduces food intake in patients with diabetes mellitus type 2. Am. J. Physiol.276: R1541-R1544. [PMID:10233049]

58. Hammer RE, Mayo KE. (1985) Expression of human growth hormone-releasing factor in transgenic mice results in increased somatic growth. Nature315: 413-416. [PMID:3923368]

59. Hansen AB, Holst JJ. (1988) Effect of truncated glucagon-like peptide 1 on cAMP in rat gastric glands and HGT-1 human gastric cancer cells. FEBS Lett.236: 119-122. [PMID:2841160]

60. Hashimoto K, Kishimoto T. (1995) Identification of alternatively spliced messenger ribonucleic acid encoding truncated growth hormone-releasing hormone receptor in human pituitary adenomas. J. Clin. Endocrinol. Metab.80: 2933-2939. [PMID:7559877]

61. Hassan HA, Heiman ML. (1995) Characterization of growth hormone-releasing hormone (GHRH) binding to cloned porcine GHRH receptor. Peptides16: 1469-1473. [PMID:8745060]

62. Hatton TW, Yip CC, Vranic M. (1985) Biosynthesis of glucagon (IRG3500) in canine gastric mucosa. Diabetes34: 38-46. [PMID:3880548]

63. Heinrich G, Gros P, Lund PK, Bentley RC, Habener JF. (1984) Pre-proglucagon messenger ribonucleic acid: Nucleotide and encoded amino acid sequences of the rat pancreatic complementary deoxyribonucleic acid. Endocrinol.115: 2176-2181. [PMID:6548696]

64. Holl RW, Leong DA. (1988) Intracellular calcium concentration and growth hormone secretion in individual somatotropes: effects of growth hormone-releasing factor and somatostatin. Endocrinology122: 2927-2932. [PMID:2453353]

65. Holz GG, Habener JF. (1993) Pancreatic β-cells are rendered glucose-competent by the insulinotropic hormone glucagon-like peptide-1(7-37). Nature361: 362-365. [PMID:8381211]

66. Holz GG, Habener JF. (1995) Activation of a cAMP-regulated Ca2+-signalling pathway in pancreatic β-cells by the insulinotropic hormone glucagon-like peptide-1. J. Biol. Chem.270: 17749-17757. [PMID:7543091]

67. Hsiung HM, Lai MH. (1993) Structure and functional expression of a complementary DNA for porcine growth hormone-releasing hormone receptor. Neuropeptides25: 1-10. [PMID:8413847]

68. Jelinek LJ, Lok S, Rosenberg GB, Smith RA, Grant FJ, Biggs S, Bensch PA, Kuijper JL, Sheppard PO, Sprecher CA. (1993) Expression cloning and signaling properties of the rat glucagon receptor. Science259 (5101): 1614-6. [PMID:8384375]

69. Kawai K, Yamashita K. (1995) Evidence that glucagon stimulates insulin secretion through its own receptor in rats. Diabetologia38: 274-276. [PMID:7758872]

70. Kieffer TJ, Pederson RA. (1995) Degradation of glucose-dependent insulinotropic polypeptide and truncated glucagon-like peptide 1 in vitro and in vivo by dipeptidyl peptidase IV. Endocrinology136: 3585-3596. [PMID:7628397]

71. Lance VA, Coy DH. (1984) Super-active analogs of growth hormone-releasing factor (1-29)-amide. Biochem. Biophys. Res. Commun.119: 265-272. [PMID:6231028]

72. Lankat-Buttgereit B, Göke B. (1994) Molecular cloning of a cDNA encoding for the GLP-1 receptor expressed in rat lung. Exp. Clin. Endocrinol.102: 341-347. [PMID:7813606]

73. Lankat-Buttgereit B, Göke B. (1997) Cloning and characterization of the 5'-flanking sequences (promoter region) of the human GLP-1 receptor gene. Peptides18: 617-624. [PMID:9213353]

74. Lin C, Rosenfeld MG. (1992) Pit-1-dependent expression of the receptor for growth hormone releasing factor mediates pituitary cell growth. Nature360: 765-768. [PMID:1334535]

75. Lin SC, Rosenfeld MG. (1993) Molecular basis of the little mouse phenotype and implications for cell type-specific growth. Nature364: 208-213. [PMID:8391647]

76. Ling N, Brazeau P. (1984) Synthesis and in vitro bioactivity of C-terminal deleted analogs of human growth hormone-releasing factor. Biochem. Biophys. Res. Commun.123: 854-861. [PMID:6435620]

77. Ling N, Guillemin R. (1984) Isolation, primary structure, and synthesis of human hypothalamic somatocrinin: growth hormone-releasing factor. Proc. Natl. Acad. Sci. U.S.A.81: 4302-4306. [PMID:6431406]

78. Lok S, Kuijper JL, Jelinek LJ, Kramer JM, Whitmore TE, Sprecher CA, Mathewes S, Grant FJ, Biggs SH, Rosenberg GB et al.. (1994) The human glucagon receptor encoding gene: structure, cDNA sequence and chromosomal localization. Gene140 (2): 203-9. [PMID:8144028]

79. Lu M, Boyd AE. (1993) The role of the free cytoplasmic calcium level in β-cell signal transduction by gastric inhibitory polypeptide and glucagon-like peptide I(7-37). Endocrinology132: 94-100. [PMID:8380389]

80. Lussier BT, Kraicer J. (1991) Free intracellular Ca2+ concentration ([Ca2+]i) and growth hormone release from purified rat somatotrophs. I. GH-releasing factor-induced Ca2+ influx raises [Ca2+]i. Endocrinology128: 570-582. [PMID:1846113]

81. MacNeil DJ, Graziano MP. (1994) Cloning and expression of a human glucagon receptor. Biochem. Biophys. Res. Commun.198: 328-334. [PMID:7507321]

82. Margioris AN, Chrousos GP. (1990) Expression and localization of growth hormone-releasing hormone messenger ribonucleic acid in rat placenta: in vitro secretion and regulation of its peptide product. Endocrinology126: 151-158. [PMID:2104584]

83. Matsubara S, Takahara J. (1995) Differential gene expression of growth hormone (GH)-releasing hormone (GRH) and GRH receptor in various rat tissues. Endocrinology136: 4147-4150. [PMID:7649123]

84. Mayo KE. (1992) Molecular cloning and expression of a pituitary-specific receptor for growth hormone-releasing hormone. Mol. Endocrinol.6: 1734-1744. [PMID:1333056]

85. Mayo KE, Evans RM. (1983) Expression-cloning and sequence of a cDNA encoding human growth hormone- releasing factor. Nature306: 86-88. [PMID:6415488]

86. Mayo KE, Evans RM. (1985) Characterization of cDNA and genomic clones encoding the precursor to rat hypothalamic growth hormone-releasing factor. Nature314: 464-467. [PMID:3920534]

87. Mayo KE, Godfrey PA. (1996) The growth-hormone-releasing hormone receptor: signal transduction, gene expression, and physiological function in growth regulation. Ann. N.Y. Acad. Sci.805: 184-203. [PMID:8993403]

88. Mayo KE, Rahal JO. (1995) Growth hormone-releasing hormone: synthesis and signalling. Recent Prog. Horm. Res.50: 35-73. [PMID:7740167]

89. Merchenthaler I, Petrusz P. (1984) Immunocytochemical localization of growth hormone-releasing factor in the rat hypothalamus. Endocrinology114: 1082-1085. [PMID:6423368]

90. Miller TL, Mayo KE. (1999) The rat growth hormone-releasing hormone receptor gene: structure, regulation, and generation of receptor isoforms with different signalling properties. Endocrinology140: 4152-4165. [PMID:10465288]

91. Mitchell ML, Silver J. (1969) Growth-hormone release by glucagon. Lancet1: 289-290. [PMID:4178983]

92. Miyawaki K, Yamada Y, Yano H, Niwa H, Ban N, Ihara Y, Kubota A, Fujimoto S, Kajikawa M, Kuroe A et al.. (1999) Glucose intolerance caused by a defect in the entero-insular axis: a study in gastric inhibitory polypeptide receptor knockout mice. Proc. Natl. Acad. Sci. U.S.A.96 (26): 14843-7. [PMID:10611300]

93. Moens K, Heimberg H, Flamez D, Huypens P, Quartier E, Ling Z, Pipeleers D, Gremlich S, Thorens B, Schuit F. (1996) Expression and functional activity of glucagon, glucagon-like peptide I, and glucose-dependent insulinotropic peptide receptors in rat pancreatic islet cells. Diabetes45 (2): 257-61. [PMID:8549871]

94. Montrose-Rafizadeh C, Adams LG. (1997) Novel signal transduction and peptide specificity of glucagon-like peptide receptor in 3T3L1 adipocytes. J. Cell. Physiol.172: 275-283. [PMID:9284947]

95. Moore MC, Cherrington AD. (1998) Autoregulation of hepatic glucose production. Eur. J. Endocrinol.138: 240-248. [PMID:9539293]

96. Motomura T, Kasayama S. (1998) Inhibition of signal transduction by a splice variant of the growth hormone-releasing hormone receptor expressed in human pituitary adenomas. Metabolism47: 804-808. [PMID:9667225]

97. Munroe DG, Gupta AK, Kooshesh F, Vyas TB, Rizkalla G, Wang H, Demchyshyn L, Yang ZJ, Kamboj RK, Chen H et al.. (1999) Prototypic G protein-coupled receptor for the intestinotrophic factor glucagon-like peptide 2. Proc. Natl. Acad. Sci. U.S.A.96 (4): 1569-73. [PMID:9990065]

98. Mutt V, Magnusson S. (1970) Structure of porcine secretin. The amino acid sequence. Eur. J. Biochem.15: 513-519. [PMID:5465996]

99. Mühlhauser I, Koch J, Berger M. (1985) Pharmacokinetics and bioavailability of injected glucagon: differences between intramuscular, subcutaneous, and intravenous administration. Diabetes Care8 (1): 39-42. [PMID:3971846]

100. Netchine I, Amselem S. (1998) Extensive phenotypic analysis of a family with growth hormone (GH) deficiency caused by a mutation in the GH-releasing hormone receptor gene. J. Clin. Endocrinol. Metab.83: 432-436. [PMID:9467553]

101. Nilsson A, Mutt V. (1980) Isolation and characterization of chicken secretin. Eur. J. Biochem.112: 383-388. [PMID:7460928]

102. Ohlsson L, Lindstrom P. (1990) The correlation between calcium outflow and growth hormone release in perifused rat somatotrophs. Endocrinology126: 488-497. [PMID:1688413]

103. Petersenn S, Schulte HM. (1998) Structure and regulation of the human growth hormone-releasing hormone receptor gene. Mol. Endocrinol.12: 233-247. [PMID:9482665]

104. Pohl SL, Rodbell M. (1971) The glucagon-sensitive adenyl cyclase system in plasma membranes of rat liver. I. Properties. J. Biol. Chem.246: 1849-1856. [PMID:4993961]

105. Ramirez JL, Gracia-Navarro F. (1999) Growth hormone (GH)-releasing factor differentially activates cyclic adenosine 3', 5'-monophosphate- and inositol phosphate-dependent pathways to stimulate GH release in two porcine somatotrope subpopulations. Endocrinology140: 1752-1759. [PMID:10098512]

106. Richter G, Arnold R. (1990) Characterization of receptors for glucagon-like peptide-1(736) amide on rat lung membranes. FEBS Lett.267: 78-80. [PMID:2163902]

107. Richter G, Arnold R. (1991) Characterization of glucagon-like peptide-I(736)amide receptors of rat lung membranes by covalent cross-linking. FEBS Lett.280: 247-250. [PMID:1849486]

108. Rivier J, Vale W. (1982) Characterization of a growth hormone-releasing factor from a human pancreatic islet tumour. Nature300: 276-278. [PMID:6292724]

109. Robberecht P, Christophe J. (1985) Structural requirements for the activation of rat anterior pituitary adenylate cyclase by growth hormone-releasing factor (GRF): discovery of (N-Ac-Tyr1, D-Arg2)-GRF(129)-NH2 as a GRF antagonist on membranes. Endocrinology117: 1759-1764. [PMID:2994998]

110. Salvatori R, Hayashida CY, Aguiar-Oliveira MH, Phillips JA, Souza AH, Gondo RG, Toledo SP, Conceicão MM, Prince M, Maheshwari HG et al.. (1999) Familial dwarfism due to a novel mutation of the growth hormone-releasing hormone receptor gene. J. Clin. Endocrinol. Metab.84 (3): 917-23. [PMID:10084571]

111. Samols E, Marks V. (1966) Interrelationship of glucagon, insulin, and glucose: The insulinogenic effect of glucagon. Diabetes15: 855-865. [PMID:5957476]

112. Sawchenko PE, Vale WW. (1985) The distribution of growth-hormone-releasing factor (GRF) immunoreactivity in the central nervous system of the rat: an immunohistochemical study using antisera directed against rat hypothalamic GRF. J. Comp. Neurol.237: 100-115. [PMID:3930577]

113. Schaffalitzky de Muckadell OB, Fahrenkrug J. (1978) Secretion pattern of secretin in man: regulation by gastric acid. Gut19: 812-818. [PMID:30682]

114. Schally AV, Varga JL. (1999) Antagonistic analogs of growth hormone-releasing hormone: new potential antitumor agents. Trends Endocrinol. Metab.10: 383-391. [PMID:10542394]

115. Schirra J, Katschinski M. (1997) Differential effects of subcutaneous GLP-1 on gastric emptying, antroduodenal motility, and pancreatic function in men. Proc. Assoc. Am. Physicians109: 84-97. [PMID:9010920]

116. Schmidtler J, Dehne K, Offermanns S, Rosenthal W, Classen M, Schepp W. (1994) Stimulation of rat parietal cell function by histamine and GLP-1-(7-36) amide is mediated by Gs alpha. Am. J. Physiol.266 (5 Pt 1): G775-82. [PMID:8203524]

117. Scott RB, Meddings JB. (1998) GLP-2 augments the adaptive response to massive intestinal resection in rat. Am. J. Physiol.275: G911-G921. [PMID:9815019]

118. Shimizu I, Shima K. (1987) Identificationand localization of glucagon-like peptide-1 and its receptor in rat brain. Endocrinology121: 1076-1082. [PMID:3040376]

119. Shinomura Y, Yalow RS. (1987) Dog secretin: sequence and biologic activity. Life Sci.41: 1243-1248. [PMID:3626755]

120. Spiess J, Vale W. (1983) Characterization of rat hypothalamic growth hormone-releasing factor. Nature303: 532-535. [PMID:6406907]

121. Stefaneanu L, Kovacs K, Horvath E, Asa SL, Losinski NE, Billestrup N, Price J, Vale W. (1989) Adenohypophysial changes in mice transgenic for human growth hormone-releasing factor: a histological, immunocytochemical, and electron microscopic investigation. Endocrinology125 (5): 2710-8. [PMID:2507296]

122. Stephanou A, Lightman SL. (1991) Production of a growth hormone-releasing hormone-like peptide and its mRNA by human lymphocytes. Neuroendocrinology53: 628-633. [PMID:1876239]

123. Stoffel M, Bell GI. (1993) Human glucagon-like peptide-1 receptor gene: Localization to chromosome band 6p21 by fluorescencein situhybridization and linkage of a highly polymorphic simple tandem repeat DNA polymorphism to other markers on chromosome 6. Diabetes42: 1215-1218. [PMID:8392011]

124. Suhr ST, Mayo KE. (1989) Mouse growth-hormone-releasing hormone: precursor structure and expression in brain and placenta. Mol. Endocrinol.3: 1693-1700. [PMID:2514346]

125. Svoboda M, Christophe J. (1993) A cDNA construct allowing the expression of rat hepatic glucagon receptors. Biochem. Biophys. Res. Commun.192: 135-142. [PMID:8386505]

126. Takahashi T, Chihara K. (1995) Regional distribution of growth hormone-releasing hormone (GHRH) receptor mRNA in the rat brain. Endocrinology136: 4721-4724. [PMID:7664697]

127. Tang J, Collu R. (1995) Identification of human growth hormone-releasing hormone receptor splicing variants. J. Clin. Endocrinol. Metab.80: 2381-2387. [PMID:7629234]

128. Thorens B. (1992) Expression cloning of the pancreatic β-cell receptor for the gluco-incretin hormone glucagon-like peptide 1. Proc. Natl. Acad. Sci. U.S.A.89: 8641-8645. [PMID:1326760]

129. Thorens B, Widmann C. (1993) Cloning and functional expression of the human islet GLP-1 receptor: Demonstration that exendin-4 is an agonist and exendin-(939) an antagonist of the receptor. Diabetes42: 1678-1682. [PMID:8405712]

130. Thorens B, Widmann C. (1996) Structure and function of the glucagon-like peptide-1 receptor. in Handbook of Experimental Pharmacology Glucagon III Edited by Lefebvre PJ Springer. 255-273 [ISBN:354060989X]

131. Tsai C-H, Drucker DJ. (1997) Biological determinants of intestinotrophic properties of GLP-2 in vivo. Am. J. Physiol.272: G662-G668. [PMID:9124589]

132. Tsai C-H, Drucker DJ. (1997) Intestinal growth-promoting properties of glucagon-like peptide 2 in mice. Am. J. Physiol.273: E77-E84. [PMID:9252482]

133. Tseng CC, Wolfe MM. (1996) Postprandial stimulation of insulin release by glucose-dependent insulinotropic polypeptide (GIP). Effect of a specific glucose-dependent insulinotropic polypeptide receptor antagonist in the rat. J. Clin. Invest.98: 2440-2445. [PMID:8958204]

134. Turton MD, O'Shea D, Gunn I, Beak SA, Edwards CM, Meeran K, Choi SJ, Taylor GM, Heath MM, Lambert PD et al.. (1996) A role for glucagon-like peptide-1 in the central regulation of feeding. Nature379 (6560): 69-72. [PMID:8538742]

135. Uttenthal LO, Blazquez E. (1990) Characterization of high affinity receptors for glucagon-like peptide-1 in rat gastric glands. FEBS Lett.262: 139-141. [PMID:2156728]

136. Uttenthal LO, Blazquez E. (1992) Autoradiographic localization of receptors for glucagon-like peptide-1(736) amide in rat brain. Neuropeptides21: 143-146. [PMID:1352862]

137. Valverde I, Villanueva-Penacarillo ML. (1993) Presence and characterization of glucagon-like peptide-1(736) amide receptors in solubilized membranes of rat adipose tissue. Endocrinology132: 75-79. [PMID:8380388]

138. Van Eyll B, Lankat-Buttgereit B, Bode HP, Göke R, Göke B. (1994) Signal transduction of the GLP-1-receptor cloned from a human insulinoma. FEBS Lett.348: 7-13. [PMID:7517895]

139. Varga JL, Rekasi Z. (1999) Synthesis and biological evaluation of antagonists of growth hormone- releasing hormone with high and protracted in vivo activities. Proc. Natl. Acad. Sci. U.S.A96: 692-697. [PMID:9892695]

140. Wajnrajch MP, Leibel RL. (1994) Human growth hormone-releasing hormone receptor (GHRHR) maps to a YAC at chromosome 7p15. Mamm. Genome5: 595---. [PMID:8000149]

141. Wajnrajch MP, Leibel RL. (1996) Nonsense mutation in the human growth hormone-releasing hormone receptor causes growth failure analogous to the little (lit) mouse. Nat. Genet.12: 88-90. [PMID:8528260]

142. Wakelam MJ, Houslay MD. (1986) Activation of two signal-transduction systems in hepatocytes by glucagon. Nature323: 68-71. [PMID:3018586]

143. Wei Y, Mojsov S. (1995) Tissue-specific expression of the human receptor for glucagon-like peptide 1: brain, heart and pancreatic forms have the same deduced amino acid sequences. FEBS Lett.358: 219-224. [PMID:7843404]

144. White CM. (1999) A review of potential cardiovascular uses of intravenous glucagon administration. J. Clin. Pharmacol.39: 442-447. [PMID:10234590]

145. Widmann C, Thorens B. (1997) Internalization and homologous desensitization of the GLP-1 receptor depend on phosphorylation of the receptor carboxyl tail at the same three sites. Mol. Endocrinol.11: 1094-1102. [PMID:9212057]

146. Wildhage I, Lankat-Buttgereit B. (1999) Gene expression of the human glucagon-like peptide-1 receptor is regulated by Sp1 and Sp3. Endocrinology140: 624-631. [PMID:9927286]

147. Yada T, Nakata M. (1993) Glucagon-like peptide-1-(7-36)amide and a rise in cyclic adenosine 3', 5'-monophosphate increase cytosolic free Ca2+ in rat pancreatic β-cells by enhancing Ca2+ channel activity. Endocrinology133: 1685-1692. [PMID:8404610]

148. You CH, Chey WY. (1983) Potentiation effect of cholecystokinin-octapeptide on pancreatic bicarbonate secretion stimulated by a physiologic dose of secretin in humans. Gastroenterology85: 40-45. [PMID:6303892]

149. Yusta B, Drucker DJ. (1999) Identification of glucagon-like peptide-2 (GLP-2)-activated signalling pathways in baby hamster kidney fibroblasts expressing the rat GLP-2 receptor. J. Biol. Chem.274: 30459-30467. [PMID:10521425]

150. Zarandi M, Schally AV. (1994) Synthesis and biological activities of highly potent antagonists of growth hormone-releasing hormone. Proc. Natl. Acad. Sci. U.S.A.91: 12298-12302. [PMID:7991622]

151. Zeitler P, Siriwardana G. (1998) Functional GHRH receptor carboxyl terminal isoforms in normal and dwarf (dw) rats. J. Mol. Endocrinol.21: 363-371. [PMID:9845677]

How to cite this page

To cite this family introduction, please use the following:

Laurence J. Miller, Daniel J. Drucker, Dominique Bataille, Susan Chan, Philippe Delagrange, Burkhard Göke, Kelly E. Mayo, Bernard Thorens, Rebecca Hills.
Glucagon receptor family, introduction. Last modified on 22/05/2017. Accessed on 19/08/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://guidetopharmacology.org/GRAC/FamilyIntroductionForward?familyId=29.