Central-type benzodiazepines and the octadecaneuropeptide modulate the effects of GABA on the release of alpha-melanocyte-stimulating hormone from frog neurointermediate lobe in vitro.
The involvement of the GABA-benzodiazepine receptor complex in the regulation of melanotropin secretion has been investigated using perfused frog neurointermediate lobes. The GABAA agonist 3-amino-1 propane sulfonic acid mimicked the biphasic effect of GABA on alpha-melanocyte-stimulating hormone secretion: a brief stimulation followed by an inhibition of melanotropin secretion. The GABAA antagonist SR 95531 (10(-4) M) inhibited both stimulation and inhibition of alpha-melanocyte-stimulating hormone release induced by GABA (10(-4) M). Since the inhibitory effect of baclofen (10(-4) M) was partially antagonized by SR 95531 (10(-4) M), it appears that the GABAergic control of alpha-melanocyte-stimulating hormone release is mainly achieved through activation of GABAA receptors. GABA-induced stimulation of alpha-melanocyte-stimulating hormone release was inhibited by tetrodotoxin (10(-5) M), an Na+ -channel blocker, or nifedipine (10(-5) M), a voltage-dependent Ca2+ -channel blocker, suggesting that Na+ and Ca2+ ions are involved in the stimulatory phase of GABA action. Only central-type benzodiazepine binding site agonists such as clonazepam (10(-4) M) modified alpha-melanocyte-stimulating hormone release. In fact, clonazepam (10(-7) to 10(-5) M) led to a dose-dependent potentiation of both GABA-induced stimulation and inhibition of alpha-melanocyte-stimulating hormone release. This potentiating effect was antagonized by the GABAA antagonist SR 95531 (10(-4) M) or by the central-type benzodiazepine binding site antagonist flumazenil (10(-4) M), whereas picrotoxin (10(-4) M) abolished only the stimulatory phase.(ABSTRACT TRUNCATED AT 250 WORDS)
Tonon
M C
MC
Groupe de Recherche en Endocrinologie Moléculaire, URA CNRS 650, Université de Rouen, Mont-Saint-Aignan, France.
Adjeroud
S
S
Lamacz
M
M
Louiset
E
E
Danger
J M
JM
Desrues
L
L
Cazin
L
L
Nicolas
P
P
Vaudry
H
H
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D026261:Diazepam Binding Inhibitor; D018756:GABA Antagonists; D066298:In Vitro Techniques; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D010446:Peptide Fragments; D010904:Pituitary Gland, Posterior / Q000187:drug effects / Q000378:metabolism*; D011724:Pyridazines / Q000494:pharmacology; D011898:Ranidae; D000521:alpha-MSH / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D026261:Diazepam Binding Inhibitor; D018756:GABA Antagonists; D009479:Neuropeptides; D010446:Peptide Fragments; D011724:Pyridazines; C067529:diazepam binding inhibitor (33-50); D001569:Benzodiazepines; D005680:gamma-Aminobutyric Acid; D000521:alpha-MSH; C044796:2-(carboxy-3'-propyl)-3-amino-4-methyl-6-phenylpyridazinium chloride; C049853:gabazine