Neuronal M2 muscarinic receptor function in guinea-pig lungs is inhibited by indomethacin

Allison Fryer, O. A. Okanlami

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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 μg/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.

Original languageEnglish (US)
Pages (from-to)559-564
Number of pages6
JournalAmerican Review of Respiratory Disease
Volume147
Issue number3
StatePublished - 1993
Externally publishedYes

Fingerprint

Muscarinic M2 Receptors
Bronchoconstriction
Indomethacin
Guinea Pigs
Cyclooxygenase Inhibitors
Gallamine Triethiodide
Lung
Naproxen
Pilocarpine
Economic Inflation
Autoreceptors
Pressure
Heart Rate
Vagus Nerve
Bradycardia
Cholinergic Agents
Electric Stimulation
Aspirin
Blood Pressure

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Neuronal M2 muscarinic receptor function in guinea-pig lungs is inhibited by indomethacin. / Fryer, Allison; Okanlami, O. A.

In: American Review of Respiratory Disease, Vol. 147, No. 3, 1993, p. 559-564.

Research output: Contribution to journalArticle

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