Sodium iodide symporter, sodium-dependent multivitamin transporter and sodium-coupled monocarboxylate transporters C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

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Overview

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The sodium-iodide symporter (NIS) is an iodide transporter found principally in the thyroid gland where it mediates the accumulation of I- within thyrocytes. Transport of I- by NIS from the blood across the basolateral membrane followed by apical efflux into the colloidal lumen, mediated at least in part by pendrin (SLC22A4), and most likely not SMCT1 (SLC5A8) as once thought, provides the I- required for the synthesis of the thyroid hormones triiodothyronine (triiodothyronine) and thyroxine (T4) [1]. NIS is also expressed in the salivary glands, gastric mucosa, intestinal enterocytes and lactating breast. NIS mediates I- absorption in the intestine and I- secretion into the milk. SMVT is expressed on the apical membrane of intestinal enterocytes and colonocytes and is the main system responsible for biotin (vitamin H) and pantothenic acid (vitamin B5) uptake in humans [13]. SMVT located in kidney proximal tubule epithelial cells mediates the reabsorption of biotin and pantothenic acid. SMCT1 (SLC5A8), which transports a wide range of monocarboxylates, is expressed in the apical membrane of epithelia of the small intestine, colon, kidney, brain neurones and the retinal pigment epithelium [6]. SMCT2 (SLC5A12) also localises to the apical membrane of kidney, intestine, and colon, but in the brain and retina is restricted to astrocytes and Müller cells, respectively [6]. SMCT1 is a high-affinity transporter whereas SMCT2 is a low-affinity transporter. The physiological substrates for SMCT1 and SMCT2 are lactate (L-lactic acid and D-lactic acid), pyruvic acid, propanoic acid, and nicotinic acid in non-colonic tissues such as the kidney. SMCT1 is also likely to be the principal transporter for the absorption of nicotinic acid (vitamin B3) in the intestine and kidney [8]. In the small intestine and colon, the physiological substrates for these transporters are nicotinic acid and the short-chain fatty acids acetic acid, propanoic acid, and butyric acid that are produced by bacterial fermentation of dietary fiber [11]. In the kidney, SMCT2 is responsible for the bulk absorption of lactate because of its low-affinity/high-capacity nature. Absence of both transporters in the kidney leads to massive excretion of lactate in urine and consequently drastic decrease in the circulating levels of lactate in blood [16]. SMCT1 also functions as a tumour suppressor in the colon as well as in various other non-colonic tissues [7]. The tumour-suppressive function of SMCT1 is based on its ability to transport pyruvic acid, an inhibitor of histone deacetylases, into cells in non-colonic tissues [17]; in the colon, the ability of SMCT1 to transport butyric acid and propanoic acid, also inhibitors of histone deacetylases, underlies the tumour-suppressive function of this transporter [6-7,9]. The ability of SMCT1 to promote histone acetylase inhibition through accumulation of butyric acid and propanoic acid in immune cells is also responsible for suppression of dendritic cell development in the colon [15].

Transporters

NIS / SLC5A5 C Show summary »

SMVT / SLC5A6 C Show summary »

SMCT1 / SLC5A8 C Show summary »

SMCT2 / SLC5A12 C Show summary »

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How to cite this family page

Database page citation:

Sodium iodide symporter, sodium-dependent multivitamin transporter and sodium-coupled monocarboxylate transporters. Accessed on 22/06/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=174.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Davies JA and CGTP Collaborators (2015) The Concise Guide to PHARMACOLOGY 2015/16: Transporters. Br J Pharmacol. 172: 6110-6202.