Central-type benzodiazepines modulate GABAA receptor chloride channels in cultured pituitary melanotrophs.
The effects of gamma-aminobutyric acid (GABA) and benzodiazepines on the electrical activity of cultured frog melanotrophs were studied using the patch-clamp technique. In the cell-attached configuration, the exposure to GABA caused a blockage of the spontaneous firing. In the whole-cell configuration, with physiological chloride concentrations, GABA evoked a hyperpolarization associated with a decrease of membrane resistance, generating an inward chloride current. Clonazepam, a central-type benzodiazepine agonist, potentiated the GABA-induced current and the resulting hyperpolarization. In addition, the benzodiazepine inverse agonist Ro 19-4603 totally abolished GABA-induced hyperpolarizing chloride current. Since the pars intermedia of the frog pituitary is composed of a 'pure' population of endocrine cells enriched with GABAA receptors, our results indicate that these cells represent a valuable model in which to investigate the electrophysiological effects of ligands for the GABAA benzodiazepine receptor complex.
Louiset
E
E
European Institute for Peptide Research, CNRS URA 650, UA INSERM, University of Rouen, Mont-Saint-Aignan, France.
Valentijn
J A
JA
Vaudry
H
H
Cazin
L
L
D000818:Animals; D002478:Cells, Cultured; D018118:Chloride Channels; D002712:Chlorides / Q000494:pharmacology; D002998:Clonazepam / Q000494:pharmacology*; D004594:Electrophysiology / Q000379:methods; D007473:Ion Channels / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010902:Pituitary Gland / Q000502:physiology*; D011898:Ranidae; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D018118:Chloride Channels; D002712:Chlorides; D007473:Ion Channels; D008565:Membrane Proteins; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D002998:Clonazepam