Changes in alpha 2- and beta-adrenoceptors in hepatocytes from rats during treatment with 3'-methyl-4-dimethylaminoazobenzene.
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 led to rapid increases in [125I]iodocyanopindolol ([125I]ICYP)- and [3H]clonidine-binding sites to hepatic membranes without significant changes in the Kd values. The number or beta-adrenoceptors defined by [125I]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 alpha 2-adrenoceptor was defined by [3H]clonidine binding being selectively inhibited by an alpha 2-antagonist, yohimbine, but not by an alpha 1-antagonist, prazosin, or a beta-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 alpha 2-adrenoceptors by NE. Therefore, we noticed that the increasing pattern of the number of beta-adrenoceptors did not always parallel IPN-stimulated adenylate cyclase activity and that the increase in the number of alpha 2-adrenoceptors preceded the difference between the efficacies of IPN and NE in activating adenylate cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)
Sanae
F
F
Research Laboratory for Development of Medicine, School of Pharmacy, Hokuriku University, Kanazawa, Japan.
Kohei
K
K
Nomura
M
M
Miyamoto
K
K
D000262:Adenylyl Cyclases / Q000032:analysis*; D000818:Animals; D003000:Clonidine / Q000032:analysis / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D020120:Iodocyanopindolol; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D008749:Methyldimethylaminoazobenzene / Q000008:administration & dosage / Q000633:toxicity*; D010869:Pindolol / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D008749:Methyldimethylaminoazobenzene; D020120:Iodocyanopindolol; D010869:Pindolol; D000262:Adenylyl Cyclases; D003000:Clonidine