Monoamine neurotransmitter transport mediated by the polyspecific cation transporter rOCT1.
The polyspecific cation transporter rOCT,1 which is localized in the basolateral membrane of rat renal proximal tubules and in sinusoidal membranes of hepatocytes, was analyzed for transport of monoamine neurotransmitters. In voltage-clamp experiments with rOCT1-expressing Xenopus oocytes, superfusion with dopamine, serotonin, noradrenaline, histamine and the permanent cation acetylcholine induced saturable inwardly directed currents with apparent Km values ranging from 20 to 100 microM. Transport of dopamine was also demonstrated by uptake measurements in oocytes and in the mammalian cell line (HEK 293) which was permanently transfected with rOCT1. The high uptake rates measured in rOCT1-expressing oocytes and in transfected HEK 293 cells suggest that rOCT1 is a high capacity transporter which mediates the first step in the excretion of monoamine neurotransmitters.
Institut für Physiologie der Eberhard-Karls-Universität, Tübingen, Germany. andreas.busch@uni-tuebingen.de
A E
AE
Busch
S
S
Quester
J C
JC
Ulzheimer
V
V
Gorboulev
A
A
Akhoundova
S
S
Waldegger
F
F
Lang
H
H
Koepsell
D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism* / Q000494:pharmacology*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000502:physiology*; D002460:Cell Line; D003001:Cloning, Molecular; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006632:Histamine / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007668:Kidney; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000502:physiology*; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D027702:Organic Cation Transporter 1; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology; D014162:Transfection; D014982:Xenopus laevis
D015306:Biogenic Monoamines; D002352:Carrier Proteins; D008565:Membrane Proteins; D027702:Organic Cation Transporter 1; D011994:Recombinant Proteins; D012701:Serotonin; D006632:Histamine; D000109:Acetylcholine; D004298:Dopamine