Pirenzepine Blunts the Pulmonary Parenchymal Response to Inhaled Methacholine

• Published in: Pulmonary pharmacology (Edinburgh) Vol. 8; no. 2; pp. 123 - 129
• Main Authors: Sly, Peter D., Willet, Karen E., Kano, Sohei, Lanteri, Celia J., Wale, Janet
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.1995
• Subjects: Animals; Dogs; Dose-Response Relationship, Drug; Lung - cytology; Lung - drug effects; Methacholine Chloride - pharmacology; Methacholine, Muscarinic receptors, Dose-response curves, Tissue viscance, Respiratory mechanics, Canine; Muscarinic Agonists - pharmacology; Muscarinic Antagonists - pharmacology; Parasympatholytics - pharmacology; Pirenzepine - pharmacology; Species Specificity; Methacholine, Muscarinic receptors, Dose-response curves, Tissue viscance, Respiratory mechanics, Canine
• ISSN: 0952-0600; 1522-9637
• DOI: 10.1006/pulp.1995.1015

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 (10000 μg/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.