MYOCARDIAL BETA-ADRENERGIC RECEPTORS FROM ADRENALECTOMIZED RATS:IMPAIRED FORMATION OF HIGH-AFFINITY AGONIST-RECEPTOR COMPLEXES

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Abstract
Adrenal steroid hormones potentiate beta-adrenergic actions on the heart. Accordingly, we investigated the effects of adrenalectomy on agonist and antagonist interactions with myocardial beta-adrenergic receptors and adenylate cyclase. The affinity and number of beta-adrenergic receptor sites, both defined by the antagonist (-)pHjdihydroalprenolol, did not change after adrenalectomy. Computer modelling of agonist (-)-isoproterenol competition curves indicated the presence of two discrete receptor states with high and low affinities. After adrenalectomy, the agonist curves were shifted to the right, and the dissociation constant of the high-affinity state significantly rose from 12 to 48 nM (p50 for isoproterenol stimulation was increased significantly from 490 to 1500 nM (p<018). These resu ts suggest that adrenal steroid hormones may regulate the ability of the beta-adrenergic receptors to form a high-affinity ”coupled” state, presumably by modulating the interaction of the receptor with nucleotide regulatory proteins.