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{{Short description|Protein-coding gene in the species Homo sapiens}}
{{PBB|geneid=6581}}
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'''Solute carrier family 22 member 3''' (also referred to as '''Organic Cation Transporter 3''' and '''Extraneuronal Monoamine Transporter''') is a [[protein]] that in humans is encoded by the ''SLC22A3'' [[gene]].<ref name="pmid9632645">{{cite journal | author = 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 | year = 1998 | month = Aug | pmid = 9632645 | pmc = | doi =10.1074/jbc.273.26.15971 }}</ref><ref name="pmid9933568">{{cite journal | author = 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 | year = 1999 | month = Sep | pmid = 9933568 | pmc = | doi = 10.1006/geno.1998.5639 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: SLC22A3 solute carrier family 22 (extraneuronal monoamine transporter), member 3| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6581| accessdate = }}</ref>
{{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]].<ref name="pmid9632645" /><ref name="pmid9933568" /><ref name="entrez" />


⚫
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.<ref name="entrez" />
<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
{{PBB_Summary
| section_title =
⚫
| summary_text = 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.<ref name="entrez"/>
⚫
}}


==Distribution==
==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.<ref name="pmid19025979" /><ref name="pmid16581093" />

OCT-3 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.<ref name="pmid19025979">{{cite journal | author = 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 | year = 2009| month = Feb| pmid = 19025979 | pmc = | doi =10.1002/cne.21921 }}</ref><ref name="pmid16581093">{{cite journal | author = 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 | year = 2006| month = Jun| pmid = 16581093| pmc = | doi =10.1016/j.neuropharm.2006.01.005 }}</ref>


==Pharmacology==
==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+|MPP<sup>+</sup>]]. Capacity for transport and affinity for these substrates may vary between rat and human isoforms however.<ref name="pmid16581093" />


⚫
Transport activity of OCT3 is inhibited by recreational and pharmaceutical drugs, including [[MDMA]], [[phencyclidine]] (PCP), [[MK-801]], [[amphetamine]], [[methamphetamine]] and [[cocaine]].<ref name="pmid16581093" /> Transport is also inhibited by the chemical [[decynium-22]] and physiological concentrations of [[corticosterone]] and [[cortisol]]. K<sub>i</sub> values for decynium-22 and corticosterone inhibition of OCT3 transport are respectively 10 and 100&nbsp;times lower than K<sub>i</sub> values of OCT1 and OCT2.<ref name="pmid12110607" /> 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.
⚫
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.<ref name="pmid16581093"/>

⚫
Transport activity of OCT-3 is inhibited by recreational and pharmaceutical drugs, including MDMA, PCP, MK-801, amphetamine, methamphetamine and Cocaine.<ref name="pmid16581093"/> Transport is also inhibited by the chemical [[decynium-22]] and physiological concentrations of [[corticosterone]] and [[cortisol]]. K<sub>i</sub> values for decynium-22 and corticosterone inhibition of OCT-3 transport are respectively 10 and 100 times lower than K<sub>i</sub> values of OCT-1 and OCT-2.<ref name="pmid12110607">{{cite journal | author = 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 | year = 2002| month = Jul| pmid = 12110607 | pmc = 1573414| doi =10.1038/sj.bjp.0704785 }}</ref>


==See also==
==See also==
Line 23: Line 18:


==References==
==References==
{{reflist}}
{{reflist|refs=
<ref name="entrez">{{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}}</ref>
⚫
<ref name="pmid12110607">{{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}}</ref>
<ref name="pmid16581093">{{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| doi =10.1016/j.neuropharm.2006.01.005| s2cid = 42204368 }}</ref>
<ref name="pmid19025979">{{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 | doi =10.1002/cne.21921| s2cid = 33389900 }}</ref>
<ref name="pmid9632645">{{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 = 15971–15979 |date=Aug 1998 | pmid = 9632645 | doi =10.1074/jbc.273.26.15971| doi-access = free }}</ref>
<ref name="pmid9933568">{{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 = 209–218 |date=Sep 1999 | pmid = 9933568 | doi = 10.1006/geno.1998.5639}}</ref>
⚫
}}


==Further reading==
==Further reading==
{{refbegin | 2}}
{{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= 32776–32786 |year= 1999 |pmid= 9830022 |doi=10.1074/jbc.273.49.32776 |doi-access=free }}
{{PBB_Further_reading
*{{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= 349–351 |year= 1999 |pmid= 10196521 |doi= 10.1038/1557 |s2cid=8355270 }}
| citations =
*{{cite journal | author=Wu X, Kekuda R, Huang W, ''et al.'' |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, Schömig E |title=Gene structures of the human non-neuronal monoamine transporters EMT and OCT2. |journal=Hum. Genet. |volume=106 |issue= 6 |pages= 627–635 |year= 2000 |pmid= 10942111 |doi=10.1007/s004390000309 |s2cid=28444495 }}
*{{cite journal | author=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=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= 10.1152/ajprenal.2000.279.3.F449|s2cid=12385921 }}
*{{cite journal | author=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=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= 1149–1157 |year= 2001 |pmid= 11129104 |doi=10.1007/s007020070028 |s2cid=9706545 }}
*{{cite journal | author=Wu X, Huang W, Ganapathy ME, ''et al.'' |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=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= 951–956 |year= 2001 |pmid= 11682442 |doi= 10.1038/sj.bjp.0704335 | pmc=1573028 }}
*{{cite journal | author=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 (Vienna, Austria : 1996) |volume=107 |issue= 10 |pages= 1149–57 |year= 2001 |pmid= 11129104 |doi=10.1007/s007020070028 }}
*{{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-Schmiedeberg's Arch. Pharmacol. |volume=364 |issue= 6 |pages= 487–495 |year= 2002 |pmid= 11770002 |doi=10.1007/s002100100476 |s2cid=21499579 }}
*{{cite journal | author=Wessler I, Roth E, Deutsch C, ''et al.'' |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=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 |year= 2003 |pmid= 12110607 |doi= 10.1038/sj.bjp.0704785 | pmc=1573414 }}
*{{cite journal | author=Martel F, Keating E, Calhau C, ''et al.'' |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=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= 810–817 |year= 2003 |pmid= 12538837 |doi= 10.1124/jpet.102.044404 |s2cid=11496882 }}
*{{cite journal | author=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=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= 226–230 |year= 2003 |pmid= 12768439 |doi= 10.1007/s10038-003-0015-5 |doi-access= free }}
*{{cite journal | author=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=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= 291–297 |year= 2004 |pmid= 14690517 |doi=10.1111/j.1471-4159.2004.02180.x |s2cid=45854898 |doi-access=free }}
*{{cite journal | author=Lazar A, Gründemann D, Berkels R, ''et al.'' |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=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= 40–45 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 |doi-access= free }}
*{{cite journal | author=Haag C, Berkels R, Gründemann D, ''et al.'' |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= }}
*{{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= 518–529 |year= 2004 |pmid= 15135235 |doi= 10.1016/j.placenta.2003.10.017 }}
*{{cite journal | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |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=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= 6496–6508 |year= 2005 |pmid= 16024787 |doi= 10.1128/MCB.25.15.6496-6508.2005 | pmc=1190334 }}
*{{cite journal | author=Bottalico B, Larsson I, Brodszki J, ''et al.'' |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=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= 1288–1297 |year= 2006 |pmid= 16141367 |doi= 10.1124/jpet.105.091223 |s2cid=1633259 }}
*{{cite journal | author=Jiang W, Prokopenko O, Wong L, ''et al.'' |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=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= 1644–1649 |year= 2006 |pmid= 17010131 |doi= 10.1111/j.1530-0277.2006.00215.x }}
*{{cite journal | author=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=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= 1303–1311 |year= 2007 |pmid= 17393420 |doi= 10.1002/mrd.20697 |s2cid=25378552 }}
*{{cite journal | author=Aoyama N, Takahashi N, Kitaichi K, ''et al.'' |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 | author=Bottalico B, Noskova V, Pilka R, ''et al.'' |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}}
{{refend}}


{{NLM content}}
{{NLM content}}
{{Membrane transport proteins}}
{{Membrane transport proteins}}

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[[Category:Solute carrier family]]
[[Category:Solute carrier family]]
[[Category:Amphetamine]]


{{membrane-protein-stub}}

Latest revision as of 14:13, 12 March 2024

SLC22A3
Identifiers
AliasesSLC22A3, EMT, EMTH, OCT3, solute carrier family 22 member 3
External IDsOMIM: 604842 MGI: 1333817 HomoloGene: 22630 GeneCards: SLC22A3
Orthologs
SpeciesHumanMouse
Entrez

6581

20519

Ensembl

ENSG00000146477

ENSMUSG00000023828

UniProt

O75751

Q9WTW5

RefSeq (mRNA)

NM_021977

NM_011395

RefSeq (protein)

NP_068812

NP_035525

Location (UCSC)Chr 6: 160.35 – 160.45 MbChr 17: 12.64 – 12.73 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[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]

Distribution[edit]

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]

Pharmacology[edit]

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.

See also[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000146477 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000023828 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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.
  6. ^ 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.
  7. ^ a b "Entrez Gene: SLC22A3 solute carrier family 22 (extraneuronal monoamine transporter), member 3".
  8. ^ 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.
  9. ^ a b c Amphoux 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.
  10. ^ 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. PMC 1573414. PMID 12110607.

Further reading[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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