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.
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.
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.
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.
^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): 15971–9. doi:10.1074/jbc.273.26.15971. PMID9632645.
^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): 209–18. doi:10.1006/geno.1998.5639. PMID9933568.
^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. PMID19025979.
^ 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. PMID16581093.
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): 32776–86. doi:10.1074/jbc.273.49.32776. PMID9830022.
Gründemann D, Schechinger B, Rappold GA, Schömig E (1999). "Molecular identification of the corticosterone-sensitive extraneuronal catecholamine transporter.". Nat. Neurosci. 1 (5): 349–51. doi:10.1038/1557. PMID10196521.
Gründemann D, Schömig E (2000). "Gene structures of the human non-neuronal monoamine transporters EMT and OCT2.". Hum. Genet. 106 (6): 627–35. doi:10.1007/s004390050035. PMID10942111.
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. PMID10966924.
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 (Vienna, Austria : 1996). 107 (10): 1149–57. doi:10.1007/s007020070028. PMID11129104.
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 Schmiedebergs Arch. Pharmacol. 364 (6): 487–95. doi:10.1007/s002100100476. PMID11770002.
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): 1303–11. doi:10.1002/mrd.20697. PMID17393420.