The benzodiazepine agonist clonazepam potentiates the effects of gamma-aminobutyric acid on alpha-MSH release from neurointermediate lobes in vitro.
The action of the central-type benzodiazepine-receptor agonist clonazepam on alpha-MSH release has been studied in vitro using perifused frog neurointermediate lobes. High concentrations of clonazepam (3.16 X 10(-5) and 10(-4) M) caused an inhibition of alpha-MSH release and this effect was reversed by the central-type benzodiazepine-receptor antagonist Ro 15-1788. High doses of GABA (10(-5) and 10(-4) M) induced a biphasic effect on pars intermedia cells: a brief stimulation followed by a sustained inhibition of alpha-MSH secretion. Administration of clonazepam (10(-5) M) in the presence of various concentrations of GABA (10(-6) to 10(-4) M) led to a potentiation of both stimulatory and inhibitory phases of alpha-MSH secretion induced by GABA. Ro 15-1788 completely abolished the potentiating effect of clonazepam. Thus our results indicate that endogenous benzodiazepine receptors may modulate the effects of GABA on alpha-MSH secretion.
D000818:Animals; D002998:Clonazepam / Q000494:pharmacology*; D004357:Drug Synergism; D005442:Flumazenil / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000378:metabolism*; D010477:Perfusion; D010904:Pituitary Gland, Posterior / Q000187:drug effects* / Q000378:metabolism; D011895:Rana ridibunda; D011963:Receptors, GABA-A / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D011963:Receptors, GABA-A; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D002998:Clonazepam; D009074:Melanocyte-Stimulating Hormones