Pirenzepine blunts the pulmonary parenchymal response to inhaled methacholine

Pulm Pharmacol. Apr-Jun 1995;8(2-3):123-9. doi: 10.1006/pulp.1995.1015.

Abstract

To determine the role of M1 muscarinic receptors in the response of the pulmonary parenchyma to inhaled methacholine (MCh), 20 mongrel, out-bred puppies, 8-10 weeks of age were challenged following pretreatment with either saline (control), UH-AH37 (a combined M1 & M3 receptor blocker), or pirenzepine (a relatively selective M1 receptor blocker). In addition, eight fox hound-beagle puppies, born and raised in a clean animal house, were studied. Relatively selective doses of pirenzepine produced a dose-dependent shift to the right of the parenchymal dose-response curves (P = 0.031), with no effect on the airway dose-response curve (P = 0.102). The fox hound-beagle puppies showed less parenchymal response (P <0.0005), but equivalent airway response (P = 0.468), to MCh compared with the mongrel puppies. High doses of pirenzepine (10 000 mu g/kg) and UH-AH37 (3 mg/kg) markedly inhibited both the parenchymal and airway responses to MCh. Data from the present study demonstrate that: (1) while both the airway and pulmonary parenchyma respond to inhaled MCh, the mechanisms by which they respond differ; (2) stimulation of M1 subtype muscarinic receptors are responsible, at least partly, for the parenchymal response; and (3) experimental conditions, such as the breed and housing conditions of animals, may have major influences on the parenchymal response to inhalational challenge tests.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dogs
  • Dose-Response Relationship, Drug
  • Lung / cytology
  • Lung / drug effects*
  • Methacholine Chloride / pharmacology*
  • Muscarinic Agonists / pharmacology*
  • Muscarinic Antagonists / pharmacology*
  • Parasympatholytics / pharmacology
  • Pirenzepine / pharmacology*
  • Species Specificity

Substances

  • Muscarinic Agonists
  • Muscarinic Antagonists
  • Parasympatholytics
  • Methacholine Chloride
  • Pirenzepine