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.
European Institute for Peptide Research, CNRS URA 650, UA INSERM, University of Rouen, Mont-Saint-Aignan, France.
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Louiset
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Valentijn
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Vaudry
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Cazin
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