title: Extraneuronal monoamine transporter and organic cation transporters 1 and 2: a review of transport efficiency.
abstract: The extraneuronal monoamine transporter (EMT) corresponds to the classical steroid-sensitive monoamine transport mechanism that was first described as "uptake2" in rat heart with noradrenaline as substrate. The organic cation transporters OCT1 and OCT2 are related to EMT. The three carriers share basic structural and functional characteristics. Hence, EMT, OCT1 and OCT2 constitute a group referred to as non-neuronal monoamine transporters or organic cation transporters. After a brief general introduction, this review focuses on the critical analysis of substrate specificity. We calculate from the available literature and compare consensus transport efficiency (clearance) data for human and rat EMT, OCT1 and OCT2, expressed in transfected cell lines. From the plethora of inhibitors that have been tested, the casual observer likely gets the impression that these carriers indiscriminately transport very many compounds. However, our knowledge about actual substrates is rather limited. 1-Methyl-4-phenylpyridinium (MPP+) is an excellent substrate for all three carriers, with clearances typically in the range of 20-50 microl min(-1) mg protein(-1). The second-best general substrate is tyramine with a transport efficiency (TE) range relative to MPP+ of 20%-70%. The TEs of OCT1 and OCT2 for dopamine, noradrenaline, adrenaline and 5-HT in general are rather low, in the range relative to MPP+ of 5%-15%. This suggests that OCT1 and OCT2 are not primarily dedicated to transport these monoamine transmitters; only EMT may play a significant role in catecholamine inactivation. For many substrates, such as tetraethylammonium, histamine, agmatine, guanidine, cimetidine, creatinine, choline and acetylcholine, the transport efficiencies are markedly different among the carriers.
authors.affiliation: Department of Pharmacology, University of Cologne, Gleueler Strasse 24, 50931 Cologne, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Schömig
authors.forename: A
authors.initials: A
authors.lastname: Lazar
authors.forename: D
authors.initials: D
authors.lastname: Gründemann
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002395:Catecholamines / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D027701:Organic Cation Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D027702:Organic Cation Transporter 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000075102:Organic Cation Transporter 2; D011487:Protein Conformation; D051381:Rats; D014162:Transfection; D014439:Tyramine / Q000378:metabolism; D000099254:Organic Cation Transporter 3
chemical_list: D015655:1-Methyl-4-phenylpyridinium; D002395:Catecholamines; D027701:Organic Cation Transport Proteins; D027702:Organic Cation Transporter 1; D000075102:Organic Cation Transporter 2; D014439:Tyramine; D000099254:Organic Cation Transporter 3; C491013:SLC22A2 protein, human; C100590:Slc22a2 protein, rat