A muscarinic receptor with high affinity for pirenzepine mediates vagally induced bronchoconstriction

John W Bloom, Henry I. Yamamura, Christine Baumgartener, Marilyn Halonen

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

The nature of the putative muscarinic receptor subtypes involved in vagally mediated bronchoconstriction wa examined in the rabbit model utilizing the classical muscarinic antagonist atropine and the selective antagonis pirenzepine. In vivo electrical stimulation of the cervical vagus nerves in anesthetized rabbits resulted in a reproducible increase in pulmonary resistance indicative of bronchoconstriction and a marked negative chronotropic effect on the heart. Both atropine and pirenzepine produced dose-related inhibition of these two vagal effects. Fify percent inhibition of the vagally induced increase in pulmonary resistance was achieved with an infusion of pirenzepine that was only 8-fold greater than the equi-effective dose of atropine. In contrast, the dose of pirenzepine required to inhibit the vagally induced decrease in heart rate by 50% was 100-fold greater than the atropine dose. Thus, pirenzepine is markedly more potent in inhibiting vagally mediated bronchoconstriction than bradycardia. In vitro inhibition of methacholine-induced contraction of bronchial rings with atropine and pirenzepine yielded pA2 values of 8.86 and 6.88 respectively (95-fold potency ratio), demonstrating that the muscarinic receptors on airway smooth muscle cells that mediate contraction are not of the pirenzepine-sensitive subtype.

Original languageEnglish (US)
Pages (from-to)21-27
Number of pages7
JournalEuropean Journal of Pharmacology
Volume133
Issue number1
DOIs
StatePublished - Jan 6 1987

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Pirenzepine
Bronchoconstriction
Muscarinic Receptors
Atropine
Rabbits
Lung
Muscarinic Antagonists
Vagus Nerve
Methacholine Chloride
Bradycardia
Electric Stimulation
Smooth Muscle Myocytes
Heart Rate

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

A muscarinic receptor with high affinity for pirenzepine mediates vagally induced bronchoconstriction. / Bloom, John W; Yamamura, Henry I.; Baumgartener, Christine; Halonen, Marilyn.

In: European Journal of Pharmacology, Vol. 133, No. 1, 06.01.1987, p. 21-27.

Research output: Contribution to journalArticle

Bloom, John W ; Yamamura, Henry I. ; Baumgartener, Christine ; Halonen, Marilyn. / A muscarinic receptor with high affinity for pirenzepine mediates vagally induced bronchoconstriction. In: European Journal of Pharmacology. 1987 ; Vol. 133, No. 1. pp. 21-27.
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