Solute carrier family 22 member 3 (SLC22A3) also known as the organic cation transporter 3 (OCT3) or extraneuronal monoamine transporter (EMT) is a protein that in humans is encoded by the SLC22A3gene.[5][6][7]
Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein.[7]
Distributionedit
OCT3 is widely distributed in brain tissue. It is not yet completely clear whether its location is primarily neuronal or glial. Areas of the brain in which it has been reported include: hippocampus, retrosplenial cortex, visual cortex, hypothalamus, amygdala, nucleus accumbens, thalamus, raphe nucleus, subiculum, superior and inferior colliculi, and islands of Calleja.[8][9]
Pharmacologyedit
Organic cation transporter 3 is a polyspecific transporter whose transport is independent of sodium. Known substrates for transport include: histamine, serotonin, norepinephrine, dopamine and MPP+. Capacity for transport and affinity for these substrates may vary between rat and human isoforms however.[9]
Transport activity of OCT3 is inhibited by recreational and pharmaceutical drugs, including MDMA, phencyclidine (PCP), MK-801, amphetamine, methamphetamine and cocaine.[9] Transport is also inhibited by the chemical decynium-22 and physiological concentrations of corticosterone and cortisol. Ki values for decynium-22 and corticosterone inhibition of OCT3 transport are respectively 10 and 100 times lower than Ki values of OCT1 and OCT2.[10] This effect of glucocorticoids is believed to explain the phenomenon of stress-induced relapse in recovering addicts, where dopamine transport inhibition causes reactivation of hypersensitive dopamine pathways involved in drug-seeking behavior and incentive salience.
^ abcGRCh38: Ensembl release 89: ENSG00000146477 – Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000023828 – Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Kekuda R, Prasad PD, Wu X, Wang H, Fei YJ, Leibach FH, Ganapathy V (Aug 1998). "Cloning and functional characterization of a potential-sensitive, polyspecific organic cation transporter (OCT3) most abundantly expressed in placenta". J Biol Chem. 273 (26): 15971–15979. doi:10.1074/jbc.273.26.15971. PMID 9632645.
^Verhaagh S, Schweifer N, Barlow DP, Zwart R (Sep 1999). "Cloning of the mouse and human solute carrier 22a3 (Slc22a3/SLC22A3) identifies a conserved cluster of three organic cation transporters on mouse chromosome 17 and human 6q26-q27". Genomics. 55 (2): 209–218. doi:10.1006/geno.1998.5639. PMID 9933568.
^ ab"Entrez Gene: SLC22A3 solute carrier family 22 (extraneuronal monoamine transporter), member 3".
^Gasser PJ, Orchinik M, Raju I, Lowry CA (Feb 2009). "Distribution of organic cation transporter 3, a corticosterone-sensitive monoamine transporter, in the rat brain". J Comp Neurol. 512 (4): 529–555. doi:10.1002/cne.21921. PMID 19025979. S2CID 33389900.
^ abcAmphoux A, Vialou V, Drescher E, Brüss M, Mannoury La Cour C, Rochat C, Millan MJ, Giros B, Bönisch H, Gautron S (Jun 2006). "Differential pharmacological in vitro properties of organic cation transporters and regional distribution in rat brain". Neuropharmacology. 50 (8): 941–952. doi:10.1016/j.neuropharm.2006.01.005. PMID 16581093. S2CID 42204368.
^Hayer-Zillgen M, Brüss M, Bönisch H (Jul 2002). "Expression and pharmacological profile of the human organic cation transporters hOCT1, hOCT2 and hOCT3". Br J Pharmacol. 136 (6): 829–836. doi:10.1038/sj.bjp.0704785. PMC1573414. PMID 12110607.
Further readingedit
Wu X, Kekuda R, Huang W, et al. (1999). "Identity of the organic cation transporter OCT3 as the extraneuronal monoamine transporter (uptake2) and evidence for the expression of the transporter in the brain". J. Biol. Chem. 273 (49): 32776–32786. doi:10.1074/jbc.273.49.32776. PMID 9830022.
Gründemann D, Schechinger B, Rappold GA, Schömig E (1999). "Molecular identification of the corticosterone-sensitive extraneuronal catecholamine transporter". Nat. Neurosci. 1 (5): 349–351. doi:10.1038/1557. PMID 10196521. S2CID 8355270.
Gründemann D, Schömig E (2000). "Gene structures of the human non-neuronal monoamine transporters EMT and OCT2". Hum. Genet. 106 (6): 627–635. doi:10.1007/s004390000309. PMID 10942111. S2CID 28444495.
Wu X, Huang W, Ganapathy ME, et al. (2000). "Structure, function, and regional distribution of the organic cation transporter OCT3 in the kidney". Am. J. Physiol. Renal Physiol. 279 (3): F449–58. doi:10.1152/ajprenal.2000.279.3.F449. PMID 10966924. S2CID 12385921.
Wieland A, Hayer-Zillgen M, Bönisch H, Brüss M (2001). "Analysis of the gene structure of the human (SLC22A3) and murine (Slc22a3) extraneuronal monoamine transporter". Journal of Neural Transmission. 107 (10): 1149–1157. doi:10.1007/s007020070028. PMID 11129104. S2CID 9706545.
Wessler I, Roth E, Deutsch C, et al. (2001). "Release of non-neuronal acetylcholine from the isolated human placenta is mediated by organic cation transporters". Br. J. Pharmacol. 134 (5): 951–956. doi:10.1038/sj.bjp.0704335. PMC1573028. PMID 11682442.
Martel F, Keating E, Calhau C, et al. (2002). "Regulation of human extraneuronal monoamine transporter (hEMT) expressed in HEK293 cells by intracellular second messenger systems". Naunyn-Schmiedeberg's Arch. Pharmacol. 364 (6): 487–495. doi:10.1007/s002100100476. PMID 11770002. S2CID 21499579.
Hayer-Zillgen M, Brüss M, Bönisch H (2003). "Expression and pharmacological profile of the human organic cation transporters hOCT1, hOCT2 and hOCT3". Br. J. Pharmacol. 136 (6): 829–836. doi:10.1038/sj.bjp.0704785. PMC1573414. PMID 12110607.
Gründemann D, Hahne C, Berkels R, Schömig E (2003). "Agmatine is efficiently transported by non-neuronal monoamine transporters extraneuronal monoamine transporter (EMT) and organic cation transporter 2 (OCT2)". J. Pharmacol. Exp. Ther. 304 (2): 810–817. doi:10.1124/jpet.102.044404. PMID 12538837. S2CID 11496882.
Lazar A, Gründemann D, Berkels R, et al. (2003). "Genetic variability of the extraneuronal monoamine transporter EMT (SLC22A3)". J. Hum. Genet. 48 (5): 226–230. doi:10.1007/s10038-003-0015-5. PMID 12768439.
Haag C, Berkels R, Gründemann D, et al. (2004). "The localisation of the extraneuronal monoamine transporter (EMT) in rat brain". J. Neurochem. 88 (2): 291–297. doi:10.1111/j.1471-4159.2004.02180.x. PMID 14690517. S2CID 45854898.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–45. doi:10.1038/ng1285. PMID 14702039.
Bottalico B, Larsson I, Brodszki J, et al. (2004). "Norepinephrine transporter (NET), serotonin transporter (SERT), vesicular monoamine transporter (VMAT2) and organic cation transporters (OCT1, 2 and EMT) in human placenta from pre-eclamptic and normotensive pregnancies". Placenta. 25 (6): 518–529. doi:10.1016/j.placenta.2003.10.017. PMID 15135235.
Jiang W, Prokopenko O, Wong L, et al. (2005). "IRIP, a new ischemia/reperfusion-inducible protein that participates in the regulation of transporter activity". Mol. Cell. Biol. 25 (15): 6496–6508. doi:10.1128/MCB.25.15.6496-6508.2005. PMC1190334. PMID 16024787.
Bourdet DL, Pritchard JB, Thakker DR (2006). "Differential substrate and inhibitory activities of ranitidine and famotidine toward human organic cation transporter 1 (hOCT1; SLC22A1), hOCT2 (SLC22A2), and hOCT3 (SLC22A3)". J. Pharmacol. Exp. Ther. 315 (3): 1288–1297. doi:10.1124/jpet.105.091223. PMID 16141367. S2CID 1633259.
Aoyama N, Takahashi N, Kitaichi K, et al. (2006). "Association between gene polymorphisms of SLC22A3 and methamphetamine use disorder". Alcohol. Clin. Exp. Res. 30 (10): 1644–1649. doi:10.1111/j.1530-0277.2006.00215.x. PMID 17010131.
Bottalico B, Noskova V, Pilka R, et al. (2007). "The organic cation transporters (OCT1, OCT2, EMT) and the plasma membrane monoamine transporter (PMAT) show differential distribution and cyclic expression pattern in human endometrium and early pregnancy decidua". Mol. Reprod. Dev. 74 (10): 1303–1311. doi:10.1002/mrd.20697. PMID 17393420. S2CID 25378552.
