Jun Shibuya, Mitsumasa Ohyanagi, Kiyoko Nakamura, Juro Yamamoto and Tadaaki
Iwasaki
First Department of Internal Medicine, Hyogo College of Medicine, Mukogawa-cho,
Nishinomiya 663-8131, Japan
Abstract: 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 imal
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.
Keywords: G protein, Heart failure, BIO 53.58 hamster, Adriamycin