Inhibition of a gamma aminobutyric acid A receptor by caffeine.
The effect of caffeine was studied on the progress of gamma aminobutyric acid A receptor channel (GABAAR) mediated transmembrane 36Cl-flux and [3H]GABA release in native membrane vesicles from rat cerebral cortex using rapid kinetic techniques. GABA response on the second time-scale mediated by the slower desensitizing GABAAR was inactivated by 5 mM caffeine whereas subsecond GABA response retained activity. An inhibitor of caffeine-evoked GABA release, dantrolene (0.025 mM), inhibited the effect of caffeine on GABA-mediated transmembrane 36Cl- ion flux. The caffeine-evoked GABA release indicated a rise of [Ca2+]i near to completion within 0.2 s. It can be assumed that elevated [Ca2+]i during depolarization and inhibition of GABAAR with longer mean lifetime function together resulting in a disinhibition of neurotransmission.
Kardos
J
J
Department of Molecular Pharmacology, Central Research Institute for Chemistry, Hungarian Academy of Sciences, Budapest.
Blandl
T
T
D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D002713:Chlorine; D003620:Dantrolene / Q000494:pharmacology; D005445:Flunitrazepam / Q000493:pharmacokinetics; D058787:GABA-A Receptor Antagonists; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D011868:Radioisotopes; D051381:Rats; D017208:Rats, Wistar
D002712:Chlorides; D058787:GABA-A Receptor Antagonists; D011868:Radioisotopes; D002110:Caffeine; D002713:Chlorine; D005445:Flunitrazepam; D003620:Dantrolene