The mechanism of action of cyproheptadine on prolactin release by cultured anterior pituitary cells.
The role of a direct effect of serotonin (5-HT) on PRL secretion at the pituitary level is uncertain. The present study investigated the mechanism of action of the serotonin receptor-blocking agent cyproheptadine on PRL release by normal cultured rat anterior pituitary cells. Cyproheptadine (10 nM-10 microM) and its metabolite desmethylcyproheptadine (a compound which has lost its affinity for serotonin receptors) directly inhibited PRL release, while serotonin, investigated over a wide concentration range, did not reverse this inhibition. The cyproheptadine-mediated inhibition of PRL-release could be completely prevented by 50 microM verapamil. Cyproheptadine strongly inhibited TRH-induced PRL release in the absence, but not in the presence of verapamil. Our studies suggest that cyproheptadine inhibits PRL release at the pituitary level by a blockade of calcium influx at the cell membrane, without affecting the movement of Ca2+ between intracellular compartments.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003533:Cyproheptadine / Q000494:pharmacology*; D005260:Female; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
D003533:Cyproheptadine; D013973:Thyrotropin-Releasing Hormone; D011388:Prolactin; D002118:Calcium