Skip to main content

Negative antagonists promote an inactive conformation of the beta 2-adrenergic receptor.

Publication ,  Journal Article
Samama, P; Pei, G; Costa, T; Cotecchia, S; Lefkowitz, RJ
Published in: Mol Pharmacol
March 1994

The beta 2-adrenergic receptor undergoes isomerization between an inactive conformation (R) and an active conformation (R*). The formation of the active conformation of the receptor molecule can be promoted by adrenergic agonists or by mutations in the third cytoplasmic domain that constitutively activate the receptor. Here we show that, of several beta-adrenergic receptor-blocking drugs tested, only two, ICI 118551 and betaxolol, inhibit the basal signaling activity of the beta 2-adrenergic receptor, thus acting as negative antagonists. We document the molecular properties of the more efficacious ICI 118551; (i) it shows higher affinity for the inactive form of the receptor and (ii) it inhibits the spontaneous formation of a beta-adrenergic receptor kinase substrate by the receptor. These properties are opposite those of adrenergic agonists, indicating that, in a fashion reciprocal to that of agonists, negative antagonists promote the formation of an inactive conformation of the receptor.

Duke Scholars

Published In

Mol Pharmacol

ISSN

0026-895X

Publication Date

March 1994

Volume

45

Issue

3

Start / End Page

390 / 394

Location

United States

Related Subject Headings

  • Signal Transduction
  • Receptors, Adrenergic, beta
  • Protein Conformation
  • Propanolamines
  • Phosphorylation
  • Pharmacology & Pharmacy
  • Lepidoptera
  • Cricetinae
  • CHO Cells
  • Binding Sites
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Samama, P., Pei, G., Costa, T., Cotecchia, S., & Lefkowitz, R. J. (1994). Negative antagonists promote an inactive conformation of the beta 2-adrenergic receptor. Mol Pharmacol, 45(3), 390–394.
Samama, P., G. Pei, T. Costa, S. Cotecchia, and R. J. Lefkowitz. “Negative antagonists promote an inactive conformation of the beta 2-adrenergic receptor.Mol Pharmacol 45, no. 3 (March 1994): 390–94.
Samama P, Pei G, Costa T, Cotecchia S, Lefkowitz RJ. Negative antagonists promote an inactive conformation of the beta 2-adrenergic receptor. Mol Pharmacol. 1994 Mar;45(3):390–4.
Samama, P., et al. “Negative antagonists promote an inactive conformation of the beta 2-adrenergic receptor.Mol Pharmacol, vol. 45, no. 3, Mar. 1994, pp. 390–94.
Samama P, Pei G, Costa T, Cotecchia S, Lefkowitz RJ. Negative antagonists promote an inactive conformation of the beta 2-adrenergic receptor. Mol Pharmacol. 1994 Mar;45(3):390–394.

Published In

Mol Pharmacol

ISSN

0026-895X

Publication Date

March 1994

Volume

45

Issue

3

Start / End Page

390 / 394

Location

United States

Related Subject Headings

  • Signal Transduction
  • Receptors, Adrenergic, beta
  • Protein Conformation
  • Propanolamines
  • Phosphorylation
  • Pharmacology & Pharmacy
  • Lepidoptera
  • Cricetinae
  • CHO Cells
  • Binding Sites