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

TY - JOUR

T1 - Decreased stimulatory guanosine triphosphate binding protein in dogs with pressure-overload left ventricular failure

AU - Longabaugh, J. P.

AU - Vatner, D. E.

AU - Vatner, S. F.

AU - Homcy, C. J.

PY - 1988

Y1 - 1988

N2 - Alterations in the level and function of the stimulatory guanyl nucleotide binding protein (G(s)) 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 β-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 G(s) (G(sα)) and found a 59% reduction in the level of this protein. Further, a 50% reduction in G(s) activity was noted in a reconstitution assay utilizing membranes from the mouse S49 lymphoma cell line cyc-, which is deficient in G(s). These data suggest that, in this model of pressure-overload left ventricular failure, the acquired defect in the β-adrenergic receptor/adenylate cyclase system involves a deficiency in the coupling protein G(s). Such an abnormality may explain the decreased adrenergic responsiveness of the failing left ventricle.

AB - Alterations in the level and function of the stimulatory guanyl nucleotide binding protein (G(s)) 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 β-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 G(s) (G(sα)) and found a 59% reduction in the level of this protein. Further, a 50% reduction in G(s) activity was noted in a reconstitution assay utilizing membranes from the mouse S49 lymphoma cell line cyc-, which is deficient in G(s). These data suggest that, in this model of pressure-overload left ventricular failure, the acquired defect in the β-adrenergic receptor/adenylate cyclase system involves a deficiency in the coupling protein G(s). Such an abnormality may explain the decreased adrenergic responsiveness of the failing left ventricle.

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U2 - https://doi.org/10.1172/JCI113335

DO - https://doi.org/10.1172/JCI113335

M3 - Article

C2 - 3123520

VL - 81

SP - 420

EP - 424

JO - The Journal of clinical investigation

JF - The Journal of clinical investigation

SN - 0021-9738

IS - 2

ER -