Changes in α_2- and β-Adrenoceptors in Hepatocytes from Rats during Treatment with 3'-Methyl-4-dimethylaminoazobenzene
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概要
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A 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB) containing diet was given to 6 weeks old female Donryu rats, and the number of adrenoceptors and the response of adenylate cyclase in the hepatocytes were measured. The treatment with 3'-MeDAB Ied to rapid increases in [^<125>I]-iodocyanopindolol ([^<125>I] ICYP)- and [^3H] clonidine-binding sites to hepatic membranes without significant changes in the K_d values. The number or β-adrenoceptors defined by [^<125>I] ICYP binding sites was increased with a biphagic mode. The [^3H] clonidine binding reached a peak 2 weeks after the start of the carcinogen diet and then began a slow descent. The α_2-adrenoceptor was defined by [^3H] clonidine binding being selectively inhibited by an α_2-antagonist, yohimbine, but not by an α_1-antagonist, prazosin, or a β-antagonist propranolol. Catecholamine responsiveness to adenylate cyclase in hepatocytes also increased during treatment with 3'-MeDAB. However, the efficacy of norepinephrine (NE) in activating cyclase was lower than that of isoproterenol (IPN) during 4 to 8 weeks of the carcinogen diet. The difference between the efficacies of IPN and NE resulted from inhibiting adenylate cyclase through α_2-adrenoceptors by NE. Therefore, we noticed that the increasing pattern of the number of β-adrenoceptors did not always parallel IPN-stimulated adenylate cyclase activity and that the increase in the number of α_2-adrenoceptors preceded the difference between the efficacies of IPN and NE in activating adenylate cyclase. These findings suggest that the emergence of β- and α_2-adrenoceptors occurs before the receptors are able to be coupled with the guanine-nucleotide binding proteins in the adenylate cyclase system in the early stage of hepatocar cinogenesis induced by 3'-MeDAB.
- 公益社団法人日本薬学会の論文
著者
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Nomura Masaaki
Research Laboratory For Development Of Medicine School Of Pharmacy Hokuriku University
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Sanae F
Hokuriku Univ. Kanazawa Jpn
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Sanae Fujiko
Third Division Of Research Department Research Laboratory For Development Of Medicine School Of Phar
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Sanae Fujiko
Research Laboratory For Development Of Medicine School Of Pharmacy Hokuriku University
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Sanae Fujiko
Department Of Applied Pharmacology Faculty Of Pharmaceutical Sciences Hokuriku University
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NOMURA MOTOYUKI
Faculty of Pharmaceutical Sciences, University of Tokushima
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KOHEI Keiko
Research Laboratory for Development of Medicine, School of Pharmacy, Hokuriku University
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MIYAMOTO Kenichi
Research Laboratory for Development of Medicine, School of Pharmacy, Hokuriku University
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Kohei Keiko
Research Laboratory For Development Of Medicine School Of Pharmacy Hokuriku University
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Miyamoto K
Department Of Medical Informatics Graduate School Of Medical Science Kanazawa University
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Miyamoto K
Department Of Engineering Physics And Mechanics Kyoto University
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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 Engineering Physics and Mechanics, Kyoto University
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