β-Adrenergic receptors: Evidence for negative cooperativity

Published

Journal Article

The specific binding of [3H] (-)alprenolol to sites in frog erythrocyte membranes provides a tool for directly assessing ligand binding to adenylatecyclase coupled β-adrenergic receptors. Hill Plots of such binding data yield slopes (nH="Hill Coefficients") less than 1.0, suggesting that negatively cooperative interactions among the β-adrenergic receptors may occur. The existence of such negative cooperativity was confirmed by a direct kinetic method. The dissociation of receptor bound [3H] (-)alprenolol was studied under two conditions: 1) with dilution of the ligand-receptor complex sufficient to prevent rebinding of the dissociated tracer and 2) with this same dilution in the presence of excess unlabeled (-)alprenolol. If the sites are independent, the dissociation rates must be the same in both cases. However, the presence of (-)alprenolol increases the rate of [3H] (-)alprenolol dissociation, indicating that negatively cooperative interactions among the β-adrenergic receptor binding sites do occur. © 1975.

Full Text

Duke Authors

Cited Authors

  • Limbird, LE; Meyts, PD; Lefkowitz, RJ

Published In

Volume / Issue

  • 64 / 4

Start / End Page

  • 1160 - 1168

Electronic International Standard Serial Number (EISSN)

  • 1090-2104

International Standard Serial Number (ISSN)

  • 0006-291X

Digital Object Identifier (DOI)

  • 10.1016/0006-291X(75)90815-3

Citation Source

  • Scopus