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词条 SLC22A3
释义

  1. Distribution

  2. Pharmacology

  3. See also

  4. References

  5. Further reading

{{Infobox_gene}}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 SLC22A3 gene.[1][2][3]

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.[3]

Distribution

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.[4][5]

Pharmacology

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.[5]

Transport activity of OCT3 is inhibited by recreational and pharmaceutical drugs, including MDMA, phencyclidine (PCP), MK-801, amphetamine, methamphetamine and cocaine.[5] 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.[6]

See also

  • Solute carrier family

References

1. ^{{cite journal | vauthors = Kekuda R, Prasad PD, Wu X, Wang H, Fei YJ, Leibach FH, Ganapathy V | title = Cloning and functional characterization of a potential-sensitive, polyspecific organic cation transporter (OCT3) most abundantly expressed in placenta | journal = J Biol Chem | volume = 273 | issue = 26 | pages = 15971–9 |date=Aug 1998 | pmid = 9632645 | pmc = | doi =10.1074/jbc.273.26.15971 }}
2. ^{{cite journal | vauthors = Verhaagh S, Schweifer N, Barlow DP, Zwart R | title = 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 | journal = Genomics | volume = 55 | issue = 2 | pages = 209–18 |date=Sep 1999 | pmid = 9933568 | pmc = | doi = 10.1006/geno.1998.5639 }}
3. ^1 {{cite web | title = Entrez Gene: SLC22A3 solute carrier family 22 (extraneuronal monoamine transporter), member 3| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6581| accessdate = }}
4. ^{{cite journal | vauthors = Gasser PJ, Orchinik M, Raju I, Lowry CA | title = Distribution of organic cation transporter 3, a corticosterone-sensitive monoamine transporter, in the rat brain. | journal = J Comp Neurol| volume = 512 | issue = 4 | pages = 529–555 |date=Feb 2009| pmid = 19025979 | pmc = | doi =10.1002/cne.21921 }}
5. ^1 2 {{cite journal | vauthors = Amphoux A, Vialou V, Drescher E, Brüss M, Mannoury La Cour C, Rochat C, Millan MJ, Giros B, Bönisch H, Gautron S | title = Differential pharmacological in vitro properties of organic cation transporters and regional distribution in rat brain. | journal = Neuropharmacology| volume = 50 | issue = 8 | pages = 941–952 |date=Jun 2006| pmid = 16581093| pmc = | doi =10.1016/j.neuropharm.2006.01.005 }}
6. ^{{cite journal | vauthors = Hayer-Zillgen M, Brüss M, Bönisch H | title = Expression and pharmacological profile of the human organic cation transporters hOCT1, hOCT2 and hOCT3 | journal = Br J Pharmacol| volume = 136| issue = 6| pages = 829–836 |date=Jul 2002| pmid = 12110607 | pmc = 1573414| doi =10.1038/sj.bjp.0704785 }}

Further reading

{{refbegin | 2}}
  • {{cite journal |vauthors=Wu X, Kekuda R, Huang W, etal |title=Identity of the organic cation transporter OCT3 as the extraneuronal monoamine transporter (uptake2) and evidence for the expression of the transporter in the brain. |journal=J. Biol. Chem. |volume=273 |issue= 49 |pages= 32776–86 |year= 1999 |pmid= 9830022 |doi=10.1074/jbc.273.49.32776 }}
  • {{cite journal | vauthors=Gründemann D, Schechinger B, Rappold GA, Schömig E |title=Molecular identification of the corticosterone-sensitive extraneuronal catecholamine transporter. |journal=Nat. Neurosci. |volume=1 |issue= 5 |pages= 349–51 |year= 1999 |pmid= 10196521 |doi= 10.1038/1557 }}
  • {{cite journal | vauthors=Gründemann D, Schömig E |title=Gene structures of the human non-neuronal monoamine transporters EMT and OCT2. |journal=Hum. Genet. |volume=106 |issue= 6 |pages= 627–35 |year= 2000 |pmid= 10942111 |doi=10.1007/s004390050035 }}
  • {{cite journal |vauthors=Wu X, Huang W, Ganapathy ME, etal |title=Structure, function, and regional distribution of the organic cation transporter OCT3 in the kidney. |journal=Am. J. Physiol. Renal Physiol. |volume=279 |issue= 3 |pages= F449–58 |year= 2000 |pmid= 10966924 |doi= }}
  • {{cite journal | vauthors=Wieland A, Hayer-Zillgen M, Bönisch H, Brüss M |title=Analysis of the gene structure of the human (SLC22A3) and murine (Slc22a3) extraneuronal monoamine transporter. |journal=Journal of Neural Transmission |volume=107 |issue= 10 |pages= 1149–57 |year= 2001 |pmid= 11129104 |doi=10.1007/s007020070028 }}
  • {{cite journal |vauthors=Wessler I, Roth E, Deutsch C, etal |title=Release of non-neuronal acetylcholine from the isolated human placenta is mediated by organic cation transporters. |journal=Br. J. Pharmacol. |volume=134 |issue= 5 |pages= 951–6 |year= 2001 |pmid= 11682442 |doi= 10.1038/sj.bjp.0704335 | pmc=1573028 }}
  • {{cite journal |vauthors=Martel F, Keating E, Calhau C, etal |title=Regulation of human extraneuronal monoamine transporter (hEMT) expressed in HEK293 cells by intracellular second messenger systems. |journal=Naunyn Schmiedebergs Arch. Pharmacol. |volume=364 |issue= 6 |pages= 487–95 |year= 2002 |pmid= 11770002 |doi=10.1007/s002100100476 }}
  • {{cite journal | vauthors=Hayer-Zillgen M, Brüss M, Bönisch H |title=Expression and pharmacological profile of the human organic cation transporters hOCT1, hOCT2 and hOCT3. |journal=Br. J. Pharmacol. |volume=136 |issue= 6 |pages= 829–36 |year= 2003 |pmid= 12110607 |doi= 10.1038/sj.bjp.0704785 | pmc=1573414 }}
  • {{cite journal | vauthors=Gründemann D, Hahne C, Berkels R, Schömig E |title=Agmatine is efficiently transported by non-neuronal monoamine transporters extraneuronal monoamine transporter (EMT) and organic cation transporter 2 (OCT2). |journal=J. Pharmacol. Exp. Ther. |volume=304 |issue= 2 |pages= 810–7 |year= 2003 |pmid= 12538837 |doi= 10.1124/jpet.102.044404 }}
  • {{cite journal |vauthors=Lazar A, Gründemann D, Berkels R, etal |title=Genetic variability of the extraneuronal monoamine transporter EMT (SLC22A3). |journal=J. Hum. Genet. |volume=48 |issue= 5 |pages= 226–30 |year= 2003 |pmid= 12768439 |doi= 10.1007/s10038-003-0015-5 }}
  • {{cite journal |vauthors=Haag C, Berkels R, Gründemann D, etal |title=The localisation of the extraneuronal monoamine transporter (EMT) in rat brain. |journal=J. Neurochem. |volume=88 |issue= 2 |pages= 291–7 |year= 2004 |pmid= 14690517 |doi=10.1111/j.1471-4159.2004.02180.x }}
  • {{cite journal |vauthors=Ota T, Suzuki Y, Nishikawa T, etal |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40–5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
  • {{cite journal |vauthors=Bottalico B, Larsson I, Brodszki J, etal |title=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. |journal=Placenta |volume=25 |issue= 6 |pages= 518–29 |year= 2004 |pmid= 15135235 |doi= 10.1016/j.placenta.2003.10.017 }}
  • {{cite journal |vauthors=Jiang W, Prokopenko O, Wong L, etal |title=IRIP, a new ischemia/reperfusion-inducible protein that participates in the regulation of transporter activity. |journal=Mol. Cell. Biol. |volume=25 |issue= 15 |pages= 6496–508 |year= 2005 |pmid= 16024787 |doi= 10.1128/MCB.25.15.6496-6508.2005 | pmc=1190334 }}
  • {{cite journal | vauthors=Bourdet DL, Pritchard JB, Thakker DR |title=Differential substrate and inhibitory activities of ranitidine and famotidine toward human organic cation transporter 1 (hOCT1; SLC22A1), hOCT2 (SLC22A2), and hOCT3 (SLC22A3). |journal=J. Pharmacol. Exp. Ther. |volume=315 |issue= 3 |pages= 1288–97 |year= 2006 |pmid= 16141367 |doi= 10.1124/jpet.105.091223 }}
  • {{cite journal |vauthors=Aoyama N, Takahashi N, Kitaichi K, etal |title=Association between gene polymorphisms of SLC22A3 and methamphetamine use disorder. |journal=Alcohol. Clin. Exp. Res. |volume=30 |issue= 10 |pages= 1644–9 |year= 2006 |pmid= 17010131 |doi= 10.1111/j.1530-0277.2006.00215.x }}
  • {{cite journal |vauthors=Bottalico B, Noskova V, Pilka R, etal |title=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. |journal=Mol. Reprod. Dev. |volume=74 |issue= 10 |pages= 1303–11 |year= 2007 |pmid= 17393420 |doi= 10.1002/mrd.20697 }}
{{refend}}{{NLM content}}{{Membrane transport proteins}}

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