Stimulatory guanine nucleotide-binding protein in failing heart of hamsters and rats.
The role of the stimulatory guanine nucleotide-binding protein (Gs) in heart failure is unclear. We therefore determined the amount of protein and mRNA of Gs in the failing myocardium using two animal models: the BIO 53.58 hamster, a model of genetic cardiomyopathy, and adriamycin-treated rats (ADR rats), a model of secondary cardiomyopathy. The maximal number of myocardial beta-adrenoceptors in the BIO 53.58 hamsters as well as in the ADR rats was significantly lower than that in the respective controls, indicating that the beta-adrenoceptors were down-regulated in heart failure. Analysis by Western blot and Northern blot revealed a significant decrease in Gs protein and mRNA in the BIO 53.58 hamsters relative to the control. There were no differences in the level of Gs protein or mRNA in the ADR rats vs the controls. The functional activity of Gs was investigated by measuring adenylate cyclase activity. The activity of adenylate cyclase in response to stimulation by sodium fluoride or forskolin was decreased in the BIO 53.58 hamsters relative to control animals, whereas no differences were observed in the ADR rats vs the controls. Thus, alterations in Gs in the failing heart appear to differ according to its cause.
Shibuya
J
J
First Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Ohyanagi
M
M
Nakamura
K
K
Yamamoto
J
J
Iwasaki
T
T
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D009202:Cardiomyopathies / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D004195:Disease Models, Animal; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D051381:Rats; D011921:Rats, Inbred WKY; D011943:Receptors, Adrenergic, beta / Q000378:metabolism
D011943:Receptors, Adrenergic, beta; D019205:GTP-Binding Protein alpha Subunits, Gs; D000262:Adenylyl Cyclases