Benzodiazepine suppression of corticotropin-releasing factor (CRF)-induced beta-endorphin release from rat neurointermediate pituitary.
Dopamine and gamma-aminobutyric acid (GABA) inhibit POMC peptide release from the pituitary intermediate lobe, via interaction with D2 or GABA-A/benzodiazepine receptors. Here, we examined the effects of an antianxiety triazolobenzodiazepine, adinazolam, on corticotropin-releasing factor (CRF)-stimulated POMC peptide secretion from the rat neurointermediate pituitary. Neurointermediate lobes (NILS) were incubated with CRF (10(-7) M), then adinazolam (10(-8) or (10(-9) M) was added, with CRF remaining in the medium. Aliquots were removed at 15-min intervals and frozen for radioimmunoassay of beta-endorphin. Adinazolam alone did not significantly affect secretion as compared to controls or CRF alone. Adinazolam incubated with CRF led to significant inhibition of beta-endorphin secretion, as compared to CRF alone. In addition, adinazolam was as effective as dopamine or the CRF antagonist, alpha-helical CRF, in preventing CRF-induced beta-endorphin release. Adinazolam appears to act directly on the pituitary to suppress hormone release induced by a stress-related hypothalamic peptide.
Saland
L C
LC
Department of Anatomy, University of New Mexico School of Medicine, Albuquerque.
Carr
J A
JA
Samora
A
A
Tejeda
D
D
D000818:Animals; D014151:Anti-Anxiety Agents; D001418:Baclofen / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D001615:beta-Endorphin / Q000378:metabolism*
D014151:Anti-Anxiety Agents; D001569:Benzodiazepines; D009118:Muscimol; D001615:beta-Endorphin; D003346:Corticotropin-Releasing Hormone; D001418:Baclofen; C039668:adinazolam; D004298:Dopamine