Neuronal M2 muscarinic receptor function in guinea-pig lungs is inhibited by indomethacin.
The function of M2 muscarinic autoreceptors on pulmonary parasympathetic nerves was investigated in the absence and presence of cyclooxygenase inhibitors in vivo. Guinea pigs were anesthetized, paralyzed, and artificially ventilated. Pulmonary inflation pressure, heart rate, and blood pressure were recorded. Electrical stimulation of vagus nerves produced bronchoconstriction (measured as an increase in pulmonary inflation pressure) and bradycardia. In control guinea pigs, pilocarpine (1 to 100 micrograms/kg) given intravenously stimulated inhibitory M2 muscarinic receptors on pulmonary parasympathetic nerves, thus attenuating vagally induced bronchoconstriction. Conversely, blockade of these autoreceptors by the selective M2 antagonist gallamine (0.1 to 10 mg/kg given intravenously) potentiated vagally induced bronchoconstriction. Separate groups of animals were given either indomethacin or naproxen. These cyclooxygenase inhibitors potentiated vagally induced bronchoconstriction. Furthermore, in those animals pretreated with either indomethacin or [+] naproxen, pilocarpine did not inhibit and gallamine did not potentiate vagally induced bronchoconstriction. In the heart, the effects of pilocarpine and gallamine on M2 muscarinic receptors were not altered by either cyclooxygenase inhibitor. Neither intravenously administered indomethacin (1 mg/kg) nor [+] naproxen (5 mg/kg) altered baseline pulmonary inflation pressure or baseline heart rate in the treated guinea pigs. These studies demonstrate that inhibitory M2 muscarinic receptors on pulmonary parasympathetic nerves do not function in the presence of cyclooxygenase inhibitors. Loss of M2 receptor function may contribute to aspirin-induced airway hyperresponsiveness.
Fryer
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Department of Environmental Health Sciences, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205.
Okanlami
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OA
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology; D003864:Depression, Chemical; D004347:Drug Interactions; D004558:Electric Stimulation; D005703:Gallamine Triethiodide / Q000494:pharmacology; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D009288:Naproxen / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D010862:Pilocarpine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000502:physiology; D013237:Stereoisomerism; D014630:Vagus Nerve / Q000502:physiology
D011976:Receptors, Muscarinic; D010862:Pilocarpine; D009288:Naproxen; D000109:Acetylcholine; D005703:Gallamine Triethiodide; D007213:Indomethacin