[Comparative effect of a new calcium antagonist, BRL 40015, and verapamil on LH secretion from cultured pituitary cells].
Effects of the new calcium antagonist with antianginal properties BRL 40015 A (-1-(4-diethoxyphenyl) methyl-3,4-(dihydro-6,7 bis (methylethoxy)-isoquinoline, hydrochloride) on luteinizing hormone (LH) release from cultured rat pituitary cells were investigated and compared with those of verapamil. BRL 40015 A provoked a dose-dependent inhibition of LHRH-stimulated LH release; IC50 (50% inhibition) was found to be 2 X 10(-6)M whereas it was ten times greater with verapamil (2 X 10(-5)M). Inhibition was reversible, partially at least, when BRL 40015 A was removed from the incubation medium. Contrarily to what occurred with verapamil, an increase in extracellular Ca2+ concentration (5mM) provoked the disappearance of BRL 40015 A--induced inhibition. Such effects of BRL 40015 A were observed in absence of cytotoxicity. Thus, while confirming that Ca2+ mobilization plays an essential role in LH release, results suggest that the mechanism of action of BRL 40015 A on calcium channels is however different from that of verapamil.
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D007546:Isoquinolines / Q000494:pharmacology*; D007700:Kinetics; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D007546:Isoquinolines; C049847:diproteverine; D007986:Luteinizing Hormone; D014700:Verapamil
Action comparée d'un nouvel antagoniste calcique, le BRL 40015 A, et du vérapamil sur la sécrétion de LH à partir de cellules hypophysaires en culture.