Sodium-coupled monocarboxylate transporters in normal tissues and in cancer

Vadivel Ganapathy, Muthusamy Thangaraju, Elangovan Gopal, Pamela M. Martin, Shiro Itagaki, Seiji Miyauchi, Puttur D. Prasad

Research output: Contribution to journalShort survey

130 Citations (Scopus)

Abstract

SLC5A8 and SLC5A12 are sodium-coupled monocarboxylate transporters (SMCTs), the former being a high-affinity type and the latter a low-affinity type. Both transport a variety of monocarboxylates in a Na+-coupled manner. They are expressed in the gastrointestinal tract, kidney, thyroid, brain, and retina. SLC5A8 is localized to the apical membrane of epithelial cells lining the intestinal tract and proximal tubule. In the brain and retina, its expression is restricted to neurons and the retinal pigment epithelium. The physiologic functions of SLC5A8 include absorption of short-chain fatty acids in the colon and small intestine, reabsorption of lactate and pyruvate in the kidney, and cellular uptake of lactate and ketone bodies in neurons. It also transports the B-complex vitamin nicotinate. SLC5A12 is also localized to the apical membrane of epithelial cells lining the intestinal tract and proximal tubule. In the brain and retina, its expression is restricted to astrocytes and Müller cells. SLC5A8 also functions as a tumor suppressor; its expression is silenced in tumors of colon, thyroid, stomach, kidney, and brain. The tumor-suppressive function is related to its ability to mediate concentrative uptake of butyrate, propionate, and pyruvate, all of which are inhibitors of histone deacetylases. SLC5A8 can also transport a variety of pharmacologically relevant monocarboxylates, including salicylates, benzoate, and γ-hydroxybutyrate. Non-steroidal anti-inflammatory drugs such as ibuprofen, ketoprofen, and fenoprofen, also interact with SLC5A8. These drugs are not transportable substrates for SLC5A8, but instead function as blockers of the transporter. Relatively less is known on the role of SLC5A12 in drug transport.

Original languageEnglish (US)
Pages (from-to)193-199
Number of pages7
JournalAAPS Journal
Volume10
Issue number1
DOIs
StatePublished - Apr 4 2008

Fingerprint

Sodium
Retina
Brain
Pyruvic Acid
Kidney
Lactic Acid
Neoplasms
Thyroid Gland
Colon
Fenoprofen
Epithelial Cells
Pharmaceutical Preparations
Hydroxybutyrates
Neurons
Ketoprofen
Ketone Bodies
Vitamin B Complex
Histone Deacetylases
Membranes
Volatile Fatty Acids

Keywords

  • Gamma-hydroxybutyrate
  • Kidney/intestine
  • Monocarboxylate drugs
  • SLC5A8/SLC5A12
  • Tumor suppressor

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Sodium-coupled monocarboxylate transporters in normal tissues and in cancer. / Ganapathy, Vadivel; Thangaraju, Muthusamy; Gopal, Elangovan; Martin, Pamela M.; Itagaki, Shiro; Miyauchi, Seiji; Prasad, Puttur D.

In: AAPS Journal, Vol. 10, No. 1, 04.04.2008, p. 193-199.

Research output: Contribution to journalShort survey

Ganapathy, Vadivel ; Thangaraju, Muthusamy ; Gopal, Elangovan ; Martin, Pamela M. ; Itagaki, Shiro ; Miyauchi, Seiji ; Prasad, Puttur D. / Sodium-coupled monocarboxylate transporters in normal tissues and in cancer. In: AAPS Journal. 2008 ; Vol. 10, No. 1. pp. 193-199.
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