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Adenylate cyclase regulation in intact cultured myocardial cells

Journal Article · · Am. J. Physiol.; (United States)
OSTI ID:6219721

To examine the coupling of cardiac cell-surface ..beta..-adrenergic receptors to adenylate cyclase activation and contractile response, the authors studied this receptor-effector response system in monolayers of spontaneously contracting chick embryo ventricular cells under physiological conditions. The hydrophilic ligand /sup 3/H-CGP12177 identified uniformly high-agonist affinity ..beta..-adrenergic receptors. Isoproterenol-stimulated cyclic AMP (cAMP) accumulation with 50% effective concentration at (EC/sub 50/) = 12.1 nM and augmented contractile response with EC/sub 50/ = 6 nM under identical conditions. One micromolar isoproterenol induced receptor loss from the cell surface with t/sub 1/2/ = 13.2 min; under identical conditions cAMP content declined with t/sub 1/2/ = 13.5 min and contractile response with t/sub 1/2/ = 20.7 min. After agonist removal cAMP response recovered with t/sub 1/2/ = 15.7 min and receptors with t/sub 1/2/ = 24.7 min. Sixty minutes after agonist removal there was recovery of 52% of maximal cAMP responsiveness and 82% of the initial number of receptors; receptor occupancy was associated with 78% of initial contractile response. Agonist affinity for cell-surface receptors was changed only modestly by agonist exposure. They conclude that for this system there is relatively close coupling between high-affinity receptors, adenylate cyclase stimulation, and contractile response.

Research Organization:
Brigham and Women's Hospital, Boston, MA
OSTI ID:
6219721
Journal Information:
Am. J. Physiol.; (United States), Journal Name: Am. J. Physiol.; (United States) Vol. 252:1; ISSN AJPHA
Country of Publication:
United States
Language:
English