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 villu s, a useful model for the characterization of the non-neuronal cholinergic system. 2 Quinine, an inhibitor of organic cation transporters (OCT), reduced acety lcholine release in a reversible and concentration-dependent manner with an IC50 value of 5 muM. The maximal effect, inhibition by 99%, occurred at a concentration of 300 um. 3 Procaine (100 muM), a sodium channel blocker, and vesamicol (10 muM), an inhibitor of the vesicular acetylcholine transporter, were ineffective. 4 Corticosterone, an inhibitor of OCT subtype 1, 2 and 3 reduced acetylchol ine in a concentration-dependent manner with an IC50 value of 2 muM. 5 Substrates of OCT subtype 1, 2 and 3 (amiloride, cimetidine, guanidine, n oradrenaline, 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 oligonucl eotides (5 muM) directed against transcription of OCT1 and OCT3 reduced the release of acetylcholine, whereas OCT2 antisense oliogonucleotides were in effective. 7 It is concluded that the release of non-neuronal acetylcholine from the h uman placenta is mediated via organic cation transporters of the OCT1 and O CT3 subtype.