THE ACTION OF MITOMYCIN C ON THE INDUCTION OF CYCLIC AMP PHOSPHODIESTERASE AND THE DEVELOPMENT OF DESENSITIZATION OF ADENYLATE CYCLASE BY ISOPROTERENOL IN RAT ASCITES HEPATOMA AH130 CELLS
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概要
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The treatment of AH130 cells with isoproterenol (IPN) resulted in an increase in the activity of cyclic adenosine 3' : 5'-monophosphate (cyclic AMP) phosphodiesterase with a low K_m value and a decrease in IPN-stimulated activity of adenylate cyclase. The activity of cyclic AMP phosphodiesterase was increased by IPN in a dose-dependent manner and reached a maximal increase at 30 min after the addition of 10^<-4>M IPN. The addition of mitomycin C (MMC) at 15 min after the initiation of the treatment with IPN inhibited the increase in the activity of cyclic AMP phosphodiesterase in a dose-dependent manner. The extent of the development of desensitization, which was observed as a decrease in IPN-stimulated activity of adenylate cyclase, was dependent on the treatment time with IPN and the concentration of IPN. Desensitization was also observed as a decrease in prostaglandin E_1-stimulated activity but not in basal and NaF-stimulated activity. The combined treatment with IPN and MMC showed a higher IPN-stimulated activity of adenylate cyclase than with a single treatment with IPN. This effect resulted from the enhancement of IPN-stimulated activity of the enzyme by MMC itself. These results show that the treatment of AH130 cells with IPN caused an induction of cyclic AMP phosphodiesterase and the development of desensitization of adenylate cyclase. Since the combined treatment with MMC inhibited both phenomena, the high intracelullar cyclic AMP level appeared to be maintained by the combined treatment for a longer term than by a single treatment with IPN.
- 公益社団法人日本薬学会の論文
著者
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MIYAMOTO Kenichi
Research Laboratory for Development of Medicine, School of Pharmacy, Hokuriku University
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Miyamoto Kenichi
Department Of Hospital Pharmacy And Department Of Medicinal Informatics Graduate School Of Medical S
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Matsunaga Takayuki
Third Division Of The Research Laboratory For Development Of Medicine School Of Pharmacy Hokuriku Un
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Koshiura Ryozo
Third Division Of Research Department Research Laboratory For Development Of Medicine School Of Phar
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MATSUNAGA TAKAYUKI
Department of Pharmacology, Hokuriku University School of Pharmacy
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KOSHIURA RYOZO
Department of Pharmacology, Hokuriku University School of Pharmacy
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Miyamoto K
Department Of Medical Informatics Graduate School Of Medical Science Kanazawa University
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Koshiura R
Third Division Of Research Department Research Laboratory For Development Of Medicine School Of Phar
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Miyamoto K
Department Of Engineering Physics And Mechanics Kyoto University
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Miyamoto Kenichi
Department Of Chemistry For Materials Faculty Of Engineering And Graduate School Of Engineering Mie
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MIYAMOTO Kenichi
Department of Engineering Physics and Mechanics, Kyoto University
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