Function of pulmonary neuronal M(2) muscarinic receptors in stable chronic obstructive pulmonary disease.
Anticholinergic drugs often cause a considerable degree of bronchodilation in patients with chronic obstructive pulmonary disease (COPD). Pulmonary neuronal M(2) muscarinic receptors function to limit the magnitude of vagally induced bronchoconstriction. We hypothesized that the effectiveness of anticholinergic agents in patients with COPD may reflect increased vagal reactivity due to dysfunction of M(2) muscarinic receptors. The function of M(2) receptors and the magnitude of vagally induced bronchoconstriction were assessed in subjects with normal lung function and in subjects with COPD. A nasal cold dry air challenge was used to induce a bronchoconstriction, measured as a change in airway resistance (Raw) at 5 Hz (R5) using impulse oscillometry. In subjects with COPD R5 rose from 0.68 +/- 0.06 to 0.74 +/- 0.07 kPa/L/s after the cold dry air challenge (p < 0.01) and in the control subjects R5 rose from 0.34 +/- 0.03 to 0.39 +/- 0.03 kPa/L/s (p < 0.01). The bronchoconstriction was inhibited by pretreatment with ipratropium bromide, indicating that it was vagally mediated. In both groups of subjects pretreatment with the selective M(2) muscarinic receptor agonist pilocarpine (5 mg/ml) prevented the cold air-induced bronchoconstriction, indicating normal function of M(2) receptors. These studies indicate that M(2) muscarinic receptors are functional in subjects with stable COPD.
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Department of Medicine, University Hospital Aintree, University of Liverpool, Liverpool L9 7AL, United Kingdom.
Boonyongsunchai
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Webb
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S
Davies
L
L
Calverley
P M
PM
Costello
R W
RW
D000368:Aged; D000403:Airway Resistance; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D016022:Case-Control Studies; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D003080:Cold Temperature; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D009241:Ipratropium / Q000494:pharmacology*; D008168:Lung / Q000294:innervation*; D008173:Lung Diseases, Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D010862:Pilocarpine / Q000494:pharmacology*; D011292:Premedication; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000502:physiology*; D012907:Smoking / Q000009:adverse effects; D013147:Spirometry; D014630:Vagus Nerve / Q000187:drug effects* / Q000503:physiopathology*; D014797:Vital Capacity
D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists; D018721:Muscarinic Agonists; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D010862:Pilocarpine; D009241:Ipratropium