Nitrooxy alkyl apovincaminate modulates GABA(A) receptor in rat neocortical neurones.
We investigated the effects of VA-045 ((+)-eburnamenine-14 carboxylic acid (2-nitroxyethyl) ester) on GABA(A) receptor-mediated Cl- currents in dissociated rat cerebral cortical neurones, using a nystatin-perforated patch recording configuration. At a holding potential of - 40mV, the external application of GABA evoked an inward Cl- current with an EC50 value of 5.6 x 10(-6)M. VA-045 increased the GABA response at GABA concentrations below 3.0 x 10(-6)M. The GABA response showed a time dependent decay consisting of fast and slow components and VA-045 significantly accelerated both components. The site of action for VA-045 was considered to be different from that for benzodiazepines or barbiturates.
Munakata
M
M
Department of Physiology, Kyushu University Faculty of Medicine, Fukuoka, Japan.
Fujimoto
M
M
Akaike
N
N
Araki
H
H
D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*; D014748:Vinca Alkaloids / Q000494:pharmacology*
D018118:Chloride Channels; D018757:GABA Modulators; D011963:Receptors, GABA-A; D014665:Vasodilator Agents; D014748:Vinca Alkaloids; C081044:2-(nitrooxy)ethyl apovincaminate; D010424:Pentobarbital; D003975:Diazepam