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• W1569575643 abstract "Background and Purpose Concentrations of extracellular glycine in the CNS are regulated by two N a + / C l – ‐dependent glycine transporters, G ly T 1 and G ly T 2. Selective inhibitors of G ly T 1 have been developed for the treatment of schizophrenia, whilst selective inhibitors of GlyT2 are analgesic in animal models of pain. We have assessed a series of endogenous lipids as inhibitors of G ly T 1 and G ly T 2. Experimental Approach Human G ly T 1 and G ly T 2 were expressed in X enopus laevis oocytes, and the inhibitory actions of a series of acylcarnitines on glycine transport were measured using electrophysiological techniques. Key Results Oleoyl‐ l ‐carnitine inhibited glycine transport by G ly T 2, with an IC 50 of 340 nM, which is 15‐fold more potent than the previously identified lipid inhibitor N ‐arachidonyl‐glycine. Oleoyl‐ l ‐carnitine had a slow onset of inhibition and a slow washout. Using a series of chimeric G ly T 1/2 transporters and point mutant transporters, we have identified an isoleucine residue in extracellular loop 4 of G ly T 2 that conferred differences in sensitivity to oleoyl‐ l ‐carnitine between G ly T 2 and G ly T 1. Conclusions and Implications Oleoyl‐ l ‐carnitine is a potent non‐competitive inhibitor of G ly T 2. Previously identified G ly T 2 inhibitors show potential as analgesics and the identification of oleoyl‐ l ‐carnitine as a novel G ly T 2 inhibitor may lead to new ways of treating pain." @default.
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• W1569575643 date "2013-01-24" @default.
• W1569575643 modified "2023-10-17" @default.
• W1569575643 title "Oleoyl-<scp>l</scp>-carnitine inhibits glycine transport by GlyT2" @default.
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• W1569575643 doi "https://doi.org/10.1111/j.1476-5381.2012.02213.x" @default.
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