Inhibitory M 2 muscarinic receptors on parasympathetic nerve endings in the lungs decrease release of acetylcholine, inhibiting vagally induced bronchoconstriction. Neuronal M 2 receptor function can be studied using selective agonists and antagonists such as pilocarpine and gallamine. In pathogenfree guinea pigs indomethacin (1 mg/kg) did not alter the effect of either gallamine or pilocarpine, thus in pathogen free animals neuronal M 2 muscarinic receptors function independently of cyclooxygenase products. However, in guinea pigs infected with virus, (which causes temporary loss of M 2 receptor function), and then allowed to recover for 8 wk (to allow recovery of M 2 receptors), indomethacin prevented both gallamine's potentiation and pilocarpine's inhibition of vagally induced bronchoconstriction. This new effect of indomethacin was not blocked by the addition of a 5-lipoxygenase inhibitor, AA861. However, the selective COX II inhibitor, L-745,337, had the same effect as indomethacin. Since exposure to ozone also caused neuronal M 2 receptors to become dependent upon cyclooxygenase the effects of viral infection are likely to be due to inflammation. Thus, despite apparent recovery of normal M 2 receptor function after viral infection or ozone, linkage of these receptors is chronically altered such that they become largely dependent on the activity of COX II. ( J. Clin. Invest. 1996. 98:299-307. )

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