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. 1988 Feb;81(2):420–424. doi: 10.1172/JCI113335

Decreased stimulatory guanosine triphosphate binding protein in dogs with pressure-overload left ventricular failure.

J P Longabaugh 1, D E Vatner 1, S F Vatner 1, C J Homcy 1
PMCID: PMC329585  PMID: 3123520

Abstract

Alterations in the level and function of the stimulatory guanyl nucleotide binding protein (Gs) from the cardiac sarcolemma were examined in a canine model of heart failure. The present study is based on our previous investigations that demonstrated both a loss of beta-adrenergic agonist high-affinity binding sites and a decreased adenylate cyclase activity in sarcolemma from failing hearts. Using cholera toxin and [32P]NAD, we labeled the alpha subunit of Gs (Gs alpha) and found a 59% reduction in the level of this protein. Further, a 50% reduction in Gs activity was noted in a reconstitution assay utilizing membranes from the mouse S49 lymphoma cell line cyc-, which is deficient in Gs. These data suggest that, in this model of pressure-overload left ventricular failure, the acquired defect in the beta-adrenergic receptor/adenylate cyclase system involves a deficiency in the coupling protein Gs. Such an abnormality may explain the decreased adrenergic responsiveness of the failing left ventricle.

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Selected References

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