Viral infection induces dependence of neuronal M₂ muscarinic receptors on cyclooxygenase in guinea pig lung

Inhibitory M₂ muscarinic receptors on parasympathetic nerve endings in the lungs decrease release of acetylcholine, inhibiting vagally induced bronchoconstriction. Neuronal M₂ receptor function can be studied using selective agonists and antagonists such as pilocarpine and gallamine. In pathogen-free guinea pigs indomethacin (1 mg/kg) did not alter the effect of either gallamine or pilocarpine, thus in pathogen free animals neuronal M₂ muscarinic receptors function independently of cyclooxygenase products. However, in guinea pigs infected with virus, (which causes temporary loss of M₂ receptor function), and then allowed to recover for 8 wk (to allow recovery of M₂ 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 M₂ receptors to become dependent upon cyclooxygenase the effects of vital infection are likely to be due to inflammation. Thus, despite apparent recovery of normal M₂ receptor function after vital infection or ozone, linkage of these receptors is chronically altered such that they become largely dependent on the activity of COX II.