Myocardial beta-adrenergic receptors from adrenalectomized rats: impaired formation of high-affinity agonist-receptor complexes.

Published

Journal Article

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 (-) [3H]dihydroalprenolol, 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 (p < .001), but the dissociation constant of the low affinity state was unchanged. Although basal, maximal isoproterenol-stimulated and fluoride-stimulated adenylate cyclase activities were unaltered, the EC50 for isoproterenol stimulation was increased significantly from 490 to 1500 nM (p <.018). These results 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.

Full Text

Duke Authors

Cited Authors

  • Davies, AO; De Lean, A; Lefkowitz, RJ

Published Date

  • February 1, 1981

Published In

Volume / Issue

  • 108 / 2

Start / End Page

  • 720 - 722

PubMed ID

  • 6256161

Pubmed Central ID

  • 6256161

International Standard Serial Number (ISSN)

  • 0013-7227

Digital Object Identifier (DOI)

  • 10.1210/endo-108-2-720

Language

  • eng

Conference Location

  • United States