Down-regulation of beta-adrenoceptors and loss of Gs alpha subunit levels in ventricular myocardium of rats treated with isoproterenol.
We investigated the influence of chronic beta-adrenergic stimulation on the beta-adrenoceptor-G protein-adenylyl cyclase system in rat ventricular myocardium. The rats received twice-daily injections of 4 mg/kg isoproterenol (ISO) alone or with 8 mg/kg propranolol (PROP) for 4 days. The ISO (10 microM)-induced increase in tissue cAMP production was lower (50%) after chronic ISO treatment than in control myocardium. The beta-adrenoceptor density decreased by 43% in ventricular membranes from ISO-treated rats. Immunoblotting techniques using specific antibodies against G proteins revealed that ventricular myocardium contains three Gs alpha subunit isoforms of 45, 47 and 52kDa. ISO treatment decreased levels of the three Gs alpha subunits by a total of 40%, while no change in Gi alpha (40/41kDa) and Gcommon beta (35/36kDa) levels were found in the same membrane preparations. The antagonist PROP almost totally blocked the effects of ISO treatment on cAMP, beta-adrenoceptors and Gs alpha subunits. These results suggest that chronic beta-adrenergic stimulation causes not only down-regulation of beta-adrenoceptors, but also loss of Gs alpha subunit levels in rat ventricular myocardium.
Department of Pharmacology, School of Medicine, Sapporo Medical University, Japan.
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H
Kimura
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Miyamoto
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Ohshika
D000818:Animals; D006332:Cardiomegaly / Q000188:drug therapy / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000032:analysis*; D006352:Heart Ventricles / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D019204:GTP-Binding Proteins; D007545:Isoproterenol