Selective agents for muscarinic receptors linked to phosphoinositide breakdown

Lalita Noronha-Blob, Brendan Canning, Diane Costello, William J. Kinnier

Research output: Contribution to journalArticlepeer-review

Abstract

We examined the effects of several muscarinic agonists and antagonists on phosphoinositide breakdown (PI) and adenylate cyclase (AC) inhibition in rat cerebral cortex and heart, respectively. Acetylcholine, carbachol and methacholine behaved as full agonists in both systems. In contrast, oxotremorine and arecoline failed to stimulate PI turnover but were potent and efficacious at inhibiting AC. Among the antagonists, pirenzepine, dicyclomine, telenzepine and (R)-QNA were both potent (Ki ∼ 0.5-7.5 nM) and selective (90- to 8 500-fold) for the PI-linked (putatively M1) brain receptor. In contrast, the cardioselective and ileal-selective M2 antagonists, AF-DX 116 and hexahydrosiladifenidol, were equipotent, competitive inhibitors of both responses. The selectivity of these drugs in terms of their biochemical responses is described.

Original languageEnglish (US)
Pages (from-to)161-167
Number of pages7
JournalEuropean Journal of Pharmacology
Volume154
Issue number2
DOIs
StatePublished - Sep 13 1988
Externally publishedYes

Keywords

  • (Rat)
  • Adenylate cyclase
  • Brain
  • Heart
  • Muscarinic acetylcholine receptor antagonists (selective)
  • Phosphoinositide breakdown

ASJC Scopus subject areas

  • Pharmacology

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