Muscarinic cholinergic receptor modulation of β-adrenergic receptor affinity for catecholamines

A. M. Watanabe, M. M. McConnaughey, R. A. Strawbridge, J. W. Fleming, L. R. Jones, H. R. Besch

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Abstract

The effects of the muscarinic cholinergic agonist methacholine on affinity of β-adrenergic receptors for isoproterenol and on isoproterenol-induced stimulation of adenylate cyclase activity were assessed in canine myocardium. GTP and guanyl-5'-yl imidodiphosphate both decreased the affinity of β-adrenergic receptors for isoproterenol without altering the affinity of these receptors for propranolol. Methacholine (10 nM to 10 μM) antagonized the guanine nucleotide-induced reduction in β-adrenergic receptor affinity for isoproterenol. This effect of methacholine was reversed by atropine. The choline ester had no effect on the affinity of β-adrenergic receptors for isoproterenol in the absence of guanine nucleotides. Likewise, methacholine had no effect on the affinity of β-adrenergic receptors for propranolol, either in the presence or absence of guanine nucleotides. Methacholine also attenuated GTP-induced activation of adenylate cyclase or isoproterenol-induced activation of the enzyme in the presence of GTP. The effects of methacholine on myocardial adenylate cyclase activity were apparent only in the presence of GTP. These effects were also reversed by atropine. The choline ester had no effect on adenylate cyclase activity in the presence of guanyl-5'-yl imidodiphosphate or NaF. The results of the present study suggest that muscarinic cholinergic agonists can regulate both β-adrenergic receptors and adenylate cyclase by modulating the effects of GTP.

Original languageEnglish (US)
Pages (from-to)4833-4836
Number of pages4
JournalJournal of Biological Chemistry
Volume253
Issue number14
StatePublished - Dec 1 1978

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Watanabe, A. M., McConnaughey, M. M., Strawbridge, R. A., Fleming, J. W., Jones, L. R., & Besch, H. R. (1978). Muscarinic cholinergic receptor modulation of β-adrenergic receptor affinity for catecholamines. Journal of Biological Chemistry, 253(14), 4833-4836.