[Effect of Ca(2+)-channel antagonists on the corticoidogenesis in primary cultured bovine adrenocortical cells].
We investigated the effect of Ca(2+)-channel antagonists, Nicardipine(N), Verapamil(V) and Flunarizine(F), on the corticoidogenesis(CG) in primary cultured bovine adrenocortical cells. To examine the effect on receptor operated Ca(2+)-channel(ROC) and voltage operated Ca(2+)-channel(VOC), involved in corticoid synthesis, adrenocorticotropic hormone(ACTH) and high-K+ were used respectively. With or without the antagonists, cells were incubated at 37 degrees C for 1h in the presence of ACTH (100pM) or K+ (30mM). Corticoid was measured fluorometrically using cortisol as the standard. N and V inhibited not only ACTH-induced CG, but high K(+)-induced CG in a concentration-dependent manner. However, F inhibited only high K(+)-induced CG, and did not affect ACTH-induced CG. These inhibitions were observed at the low micromolar concentrations (below 40 microM) of the antagonists. In the regulation of corticoid synthesis, we indicate that F has an inhibitory effect on VOC without ROC; on the other hand, N and V inhibit both ROC and VOC.
Nakamichi
N
N
Department of Pharmacology I, Jikei University School of Medicine.
Tou
S
S
Murakami
M
M
Yamada
K
K
Takamura
M
M
Kawamura
M
M
D000302:Adrenal Cortex / Q000166:cytology / Q000378:metabolism*; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000324:Adrenocorticotropic Hormone / Q000037:antagonists & inhibitors; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D005444:Flunarizine / Q000494:pharmacology; D009529:Nicardipine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D000305:Adrenal Cortex Hormones; D002121:Calcium Channel Blockers; D000324:Adrenocorticotropic Hormone; D014700:Verapamil; D009529:Nicardipine; D005444:Flunarizine