Release of non-neuronal acetylcholine from the isolated human placenta is mediated by organic cation transporters.
1. The release of acetylcholine was investigated in the human placenta villus, a useful model for the characterization of the non-neuronal cholinergic system. 2. Quinine, an inhibitor of organic cation transporters (OCT), reduced acetylcholine release in a reversible and concentration-dependent manner with an IC(50) value of 5 microM. The maximal effect, inhibition by 99%, occurred at a concentration of 300 microM. 3. Procaine (100 microM), a sodium channel blocker, and vesamicol (10 microM), an inhibitor of the vesicular acetylcholine transporter, were ineffective. 4. Corticosterone, an inhibitor of OCT subtype 1, 2 and 3 reduced acetylcholine in a concentration-dependent manner with an IC(50) value of 2 microM. 5. Substrates of OCT subtype 1, 2 and 3 (amiloride, cimetidine, guanidine, noradrenaline, verapamil) inhibited acetylcholine release, whereas carnitine, a substrate of subtype OCTN2, exerted no effect. 6. Long term exposure (48 and 72 h) of villus strips to anti-sense oligonucleotides (5 microM) directed against transcription of OCT1 and OCT3 reduced the release of acetylcholine, whereas OCT2 anti-sense oliogonucleotides were ineffective. 7. It is concluded that the release of non-neuronal acetylcholine from the human placenta is mediated via organic cation transporters of the OCT1 and OCT3 subtype.
Wessler
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Department of Pharmacology, Universität Mainz, Obere Zahlbacher Strasse 67, 55101 Mainz, Germany. Wessler@mail.uni-mainz.de
Roth
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Deutsch
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Brockerhoff
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Bittinger
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Kirkpatrick
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CJ
Kilbinger
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D000109:Acetylcholine / Q000378:metabolism*; D000584:Amiloride / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D003345:Corticosterone / Q000494:pharmacology; D016373:DNA, Antisense / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D019791:Guanidine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000494:pharmacology; D027701:Organic Cation Transport Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D027702:Organic Cation Transporter 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D000075102:Organic Cation Transporter 2; D010880:Piperidines / Q000494:pharmacology; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011343:Procaine / Q000494:pharmacology; D011803:Quinine / Q000494:pharmacology; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
D016373:DNA, Antisense; D027701:Organic Cation Transport Proteins; D027702:Organic Cation Transporter 1; D000075102:Organic Cation Transporter 2; D010880:Piperidines; C491013:SLC22A2 protein, human; C006189:vesamicol; D011343:Procaine; D000584:Amiloride; D002927:Cimetidine; D011803:Quinine; D014700:Verapamil; D019791:Guanidine; D000109:Acetylcholine; D003345:Corticosterone; D009638:Norepinephrine