Effects of serotonin, cyproheptadine and reserpine on corticotropin-releasing factor release from the rat hypothalamus in vitro.
We investigated the effects of serotonin, cyproheptadine and reserpine on corticotropin-releasing factor (CRF) release from the rat hypothalamus, and the effect of cyproheptadine on CRF-induced adrenocorticotropic hormone (ACTH) secretion from the anterior pituitary (AP) in vitro using a perifusion system for rat hypothalami and AP, and a rat CRF radioimmunoassay. Cyproheptadine, 10(-8) M, had a direct inhibitory effect on both basal and 10(-9) M CRF-induced ACTH secretion from the rat AP in vitro. In addition, 10(-9)-10(-7) M cyproheptadine inhibited basal CRF release in a dose-dependent fashion, and also suppressed serotonin- and KCl-induced CRF release. Conversely, 10(-9)-10(-7) M reserpine failed to influence CRF release from the rat hypothalamus. These results indicate that a serotonergic mechanism may be involved in the CRF-releasing mechanism, and inhibition of depolarization-dependent calcium entry into cells and/or nerve endings. In addition an anti-serotonergic mechanism is involved in the inhibitory action of cyproheptadine.
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D003533:Cyproheptadine / Q000494:pharmacology*; D004347:Drug Interactions; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology*
D003533:Cyproheptadine; D012701:Serotonin; D012110:Reserpine; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D011188:Potassium