Pirenzepine Blunts the Pulmonary Parenchymal Response to Inhaled Methacholine

✍ Scribed by Peter D. Sly; Karen E. Willet; Sohei Kano; Celia J. Lanteri; Janet Wale

• Publisher: Elsevier
• Year: 1995
• Tongue: English
• Weight: 408 KB
• Volume: 8
• Category: Article
• ISSN: 0952-0600
• DOI: 10.1006/pulp.1995.1015

✦ Synopsis

SUMMARY: 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 \mu \mathrm{g} / \mathrm{kg}) ) and UH-AH37 ((3 \mathrm{mg} / \mathrm{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.