Biochemical mechanisms of myocardial adenylate cyclase subsensitivity to isoproterenol in cardiac hypertrophy of spontaneously hypertensive rats

Thesis/Dissertation · Tue Dec 31 23:00:00 EST 1985

OSTI ID:6974493

Cheon, J W

The responsiveness of the myocardial adenylate cyclase (AC) system in generating cAMP was studied using isoproterenol (a beta-adrenergic receptor agonist), cholera toxin (a guanosinetriphosphatase inhibitor) and forskolin (a catalytic unit activator) in isolated myocytes of age-matched, 14-17 weeks old Wistar Kyoto normotensive rates (WKYs) and spontaneously hypertensive rats (SHRs). We found a reduction in isoproterenol-stimulated cAMP formation in myocytes of SHRs compared with WKYs. This reduction was not due to changes in isoproterenol-receptor interactions. Scatchard plot analysis of (/sup 3/H)CGP 12177 binding to beta-adrenergic receptors in isolated myocytes of WKYs and SHRs revealed to significant differences in the maximum number of binding sites or dissociation constant. There were no significant differences in Ki and IC/sub 50/ calculated from the competitive displacement of (/sup 3/H)CGP 12177 binding by (-) isoproterenol, suggesting no change in the affinity of the beta-adrenergic receptors for isoproterenol. We found no significant differences in forskolin-stimulated cAMP formation between the two groups. This suggest that the reduction in isoproterenol-stimulated cAMP formation observed in myocytes of SHRs is not due to changes in the ability of catalytic unit to convert ATP to cAMP. Interestingly, cholera toxin-stimulated cAMP formation was increased in myocytes of SHRs. One possible explanation for these observations may be increased guanosinetriphosphatase (GTPase) activation by isoproterenol in myocytes of SHRs. The activation of GTPase by isoproterenol in myocytes of SHRs. The activation of GTPase by isoproterenol was measured as the release of Pi from (..gamma..-/sup 32/P)GTP. There was an increase in isoproterenol-stimulated GTPase activity in myocytes of SHRs compared with WKYs.

• Research Organization: Rochester Univ., NY (USA)
• OSTI ID: 6974493
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADENYLIC ACID
AMP
ANIMAL CELLS
ANIMALS
ANTIGENS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
CARDIOVASCULAR DISEASES
CARDIOVASCULAR SYSTEM
CHEMICAL ACTIVATION
CYCLASES
DAYS LIVING RADIOISOTOPES
DISEASES
DRUGS
ENZYME ACTIVITY
ENZYMES
ESTERASES
HEART
HYDROLASES
HYPERTENSION
HYPERTROPHY
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LABELLED COMPOUNDS
LIGHT NUCLEI
LYASES
MAMMALS
MATERIALS
MEMBRANE PROTEINS
NUCLEI
NUCLEOTIDASES
NUCLEOTIDES
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
PHARMACOLOGY
PHOSPHATASES
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PROTEINS
RADIOISOTOPES
RATS
REACTION KINETICS
RECEPTORS
RESPONSE MODIFYING FACTORS
RODENTS
SYMPATHOMIMETICS
SYMPTOMS
TOXIC MATERIALS
TOXINS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VASCULAR DISEASES
VERTEBRATES