Efficiency of coupling between the beta adrenergic receptor and adenylate cyclase

A. C. Howlett, P. M. Van Arsdale, A. G. Gilman

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Under experimental conditions in which the coupling between the beta adrenergic receptor and adenylate cyclase was altered in S49 lymphoma cell membranes, changes were observed in the ratio of K(D) to K(act) for beta adrenergic agonists and in the effects of guanine nucleotide on the binding of agonists. The K(D) for isoproterenol binding to the beta adrenergic receptor was greater than the K(act) for enzyme activation, despite the use of a simultaneous assay technique. The ratio of K(D) to K(act) was decreased under conditions of less efficient coupling, such as in the presence of filipin or stimulation by partial agonists. However, cholera toxin treatment, which improves coupling efficiency, increased the ratio of K(D) to K(act) for both full and partial agonists. The ability of guanine nucleotides to decrease the affinity of the beta adrenergic receptor for agonists was lost when membranes were treated with filipin or 10 mM N-ethylmaleimide. However, 1 mM N-ethylmaleimide, a concentration sufficient to inhibit over 90% of adenylate cyclase activity in this membrane preparation, was ineffective in altering the binding characteristics. The effect of guanine nucleotide can thus be observed in the absence of a functional catalytic unit of adenylate cyclase.

Original languageEnglish (US)
Pages (from-to)531-539
Number of pages9
JournalMolecular Pharmacology
Volume14
Issue number4
StatePublished - Dec 1 1978

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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