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G protein-adrenergic interactions in the heart
J P Bilezikian1, S F Steinberg, E M Horn
1Department of Medicine, College of Physicians & Surgeons, Columbia University, New York, New York 10032.
Molecular and Cellular Biochemistry
|July 1, 1988
Summary
Guanine nucleotide binding proteins (G proteins) modulate heart function during development and adaptation. Changes in G protein levels and activity are linked to altered adrenergic responses in cardiac cells and heart failure.
Area of Science:
- Cardiovascular Physiology
- Molecular Cardiology
- Neuroendocrinology
Background:
- Adrenergic signaling in the heart is crucial for regulating cardiac function.
- Guanine nucleotide-binding proteins (G proteins) mediate signal transduction pathways for many receptors, including adrenergic receptors.
- Developmental and adaptive changes can alter cardiac adrenergic responses.
Purpose of the Study:
- To investigate the role of G proteins in developmental and adaptive changes of cardiac adrenergic actions.
- To elucidate the specific G proteins involved in different cardiac responses to adrenergic agonists.
- To examine the G protein involvement in blunted adrenergic responsiveness in heart failure.
Main Methods:
- Primary cultures of rat cardiac myocytes were used to study chronotropic responses.
- ADP-ribosylation catalyzed by pertussis toxin and cholera toxin was employed to quantify G protein levels.
- Adult canine Purkinje fibers were utilized to assess automaticity changes.
- Lymphocytes from human heart failure patients were analyzed for Gs protein levels.
Main Results:
- Innervation of cardiac myocytes by sympathetic nerves shifted phenylephrine response from positive to negative chronotropy, associated with increased pertussis toxin-sensitive G protein.
- Phenylephrine-induced decrease in automaticity of canine Purkinje fibers was linked to a pertussis toxin substrate.
- Reduced G protein levels correlated with increased automaticity in Purkinje fibers.
- Congestive heart failure patients showed reduced Gs protein in lymphocytes, which normalized with therapy.
Conclusions:
- G proteins play critical roles in both developmental and adaptive adrenergic signaling in the heart.
- Specific G proteins are functionally and biochemically linked to distinct adrenergic responses, including negative chronotropy and altered automaticity.
- Dysregulation of G proteins, particularly Gs, is implicated in the pathophysiology of congestive heart failure and its therapeutic response.