Pirenzepine blunts the pulmonary parenchymal response to inhaled methacholine.
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.
Sly
P D
PD
Division of Clinical Sciences, Institute for Child Health Research, Perth, Australia.
Willet
K E
KE
Kano
S
S
Lanteri
C J
CJ
Wale
J
J
D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D008168:Lung / Q000166:cytology / Q000187:drug effects*; D016210:Methacholine Chloride / Q000494:pharmacology*; D018721:Muscarinic Agonists / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D010276:Parasympatholytics / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology*; D013045:Species Specificity
D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D016210:Methacholine Chloride; D010890:Pirenzepine