Subsensitivity of adenylate cyclase and decreased beta-adrenergic receptor binding after chronic exposure to (minus)-isoproterenol in vitro.

Journal Article (Journal Article)

In vitro incubation of frog erythrocytes with (minus)-isoproterenol, 0.1 mM, at 23 degrees for 10 to 24 hours caused a 63% decline (rho less than 0.001) in the maximum (minus)-isoproterenol-stimulated adenylate cyclase activity in the erythrocyte membranes. Affinity for (minus)-isoproterenol as judged by the concentration which half-maximally stimulated the enzyme was not markedly altered. Basal enzyme activity and stimulation by fluoride or prostaglandin E1 remained unaltered. The number of beta-adrenergic receptor binding sites, assessed by binding studies with the beta-adrenergic antagonist (minus)-[3-H] alprenolol, declined by 50% (rho less than 0.005) in the (minus)-isoproterenol-treated cells. The binding affinity of the sites was not changed. Regulation of the concentration of functionally active beta-adrenergic receptors in membranes may be one of the mechanisms by which chronic exposure to catecholamines desensitizes tissues to beta-adrenergic stimulation.

Full Text

Duke Authors

Cited Authors

  • Mickey, J; Tate, R; Lefkowitz, RJ

Published Date

  • July 25, 1975

Published In

Volume / Issue

  • 250 / 14

Start / End Page

  • 5727 - 5729

PubMed ID

  • 167023

International Standard Serial Number (ISSN)

  • 0021-9258


  • eng

Conference Location

  • United States