Diazepam potentiates the corticoidogenic response of bovine adrenal fasciculata cells to dibutyryl cyclic AMP.
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概要
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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 μM) 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 KCI. 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 <I>de novo</I> 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 <I>de novo</I> synthesis) without any change of voltage-dependent Ca channels.
- 公益社団法人 日本薬理学会の論文
著者
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Kawamura Masahiro
Department Of Pharmacology (1) The Jikei University School Of Medicine
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NAKAMICHI NOBORU
Department of Pharmacology, The Jikei University School of Medicine
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Takamura Mitsuyuki
Department Of Epidemiology And Environmental Health Juntendo University Faculty Of Medicine
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MATSUI Takashi
Department of Aquatic Bioscience, Graduate School of Agricultural and Life Sciences, The University of Tokyo
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YAMADA Kenji
Department of Applied Chemistry, Faculty of Engineering, Chiba University
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Ohno Yuji
Department of Electronic Engineering, Graduate School of Engineering, Tohoku University, Sendai 980-8579, Japan
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YANAGIBASHI Kazutoshi
Department of Pharmacology I, The Jikei University School of Medicine
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HAYASHIDA Keiko
Department of Pharmacology I, The Jikei University School of Medicine
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TOU Shohei
Department of Pharmacology I, The Jikei University School of Medicine
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Nakamichi Noboru
Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University
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TAKAMURA Mitsuyuki
Department of Pharmacology I, The Jikei University School of Medicine
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