[Abnormalities in the beta-adrenergic receptor-adenylate cyclase system in the ventricular myocardium of spontaneously hypertensive rats].
We studied the molecular mechanisms of the abnormal response of the beta-adrenergic receptor-adenylate cyclase system in the myocardium of spontaneously hypertensive rats (SHR) by ADP-ribosylation catalyzed by cholera toxin and pertussis toxin, by reconstitutive assay of cardiac membranes with the human platelet membranes, and by immunostaining with polyclonal antibody against beta gamma-subunits of guanine nucleotide-binding proteins. The maximal activity of the enzyme stimulated by forskolin was higher in SHR than in control Wistar Kyoto (WKY) rats. However, the activity stimulated by isoproterenol, glucagon, histamine was similar for SHR and control rats. Moreover, the activity stimulated by PGE1 was lower in SHR than in control rats. The activity of the stimulatory guanine nucleotide-binding protein (Gs) of cholate extracted cardiac membranes from SHR was significantly lower than that from control rats. There were no strain differences in (1) number and affinity of beta-adrenergic receptors, (2) the function and amount of the inhibitory guanine nucleotide-binding protein (Gi), (3) substrates for cholera toxin catalyzed ADP-ribosylation, and (4) the amount of beta gamma-subunits of Gs and Gi. Thus, there is an abnormal signal transduction in beta-adrenergic receptor coupled adenylate cyclase system in SHR due to a reduction in the activity of the alpha-subunits of Gs.
Murakami
T
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Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure; D002462:Cell Membrane / Q000378:metabolism; D006352:Heart Ventricles / Q000033:anatomy & histology; D008297:Male; D008970:Molecular Weight; D009206:Myocardium / Q000378:metabolism*; D009929:Organ Size; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D011943:Receptors, Adrenergic, beta; D000262:Adenylyl Cyclases