Diazepam potentiates the corticoidogenic response of bovine adrenal fasciculata cells to dibutyryl cyclic AMP.
To provide a possible role of peripheral type benzodiazepine receptors in the regulation of glucocorticoid biosynthesis. We have examined the effect of diazepam on the corticoidogenic response to dibutyryl cyclic AMP in isolated bovine adrenal fasciculata cells. Diazepam alone (up to 100 microM) had no effect on the corticoidogenesis. Diazepam caused a dose-dependent potentiation of dibutyryl cyclic AMP-induced corticoidogenesis. However, diazepam had no effect on the corticoidogenic response to ACTH and a high concentration of KCl. The potentiating effect by diazepam was clearly detected after 90 min-incubation, and it was blocked by YM-684 (diazepam antagonist) and ML-236B (cholesterol de novo synthesis inhibitor). Diazepam caused no significant decrease of intracellular content of cholesteryl esters during the corticoidogenic response to dibutyryl cyclic AMP. When the cells were incubated in the presence of (+)-PN200-110, a potent voltage-dependent Ca channel inhibitor, the potentiating effect by diazepam was not affected in spite of a significant inhibition of dibutyryl cyclic AMP-induced corticoidogenesis. These results indicate that the potentiating effect of diazepam on dibutyryl cyclic AMP-induced corticoidogenesis is due in part to the activation of the intracellular cholesterol supply system (cholesterol de novo synthesis) without any change of voltage-dependent Ca channels.
Yanagibashi
K
K
Department of Pharmacology I, Jikei University School of Medicine, Tokyo, Japan.
Ohno
Y
Y
Nakamichi
N
N
Matsui
T
T
Hayashida
K
K
Takamura
M
M
Yamada
K
K
Tou
S
S
Kawamura
M
M
D000302:Adrenal Cortex / Q000166:cytology*; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D002417:Cattle; D002788:Cholesterol Esters / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D011189:Potassium Chloride / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000502:physiology
D000305:Adrenal Cortex Hormones; D002788:Cholesterol Esters; D011963:Receptors, GABA-A; D003994:Bucladesine; D011189:Potassium Chloride; D000324:Adrenocorticotropic Hormone; D003975:Diazepam