Enhancement by Parainfluenza 3 Infection of Contractile Responses to Substance P and Capsaicin in Airway Smooth Muscle from the Guinea Pig

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Abstract
Guinea pigs were inoculated by nasal insufflation with parainfluenza 3 (P-3) or virus growth medium 4 days before performing in vitro pharmacologic studies on left bronchial ring segments. Cumulative dose-response studies with capsaicin revealed an enhanced contractile response after P-3 infection. The sensitivity and magnitude of contractile effects of substance P in the left bronchi were also enhanced by P-3 infection. After pretreatment of the isolated tissues with phenoxybenzamine to block histamine H1 (with metiamide to block histamine H2), muscarinic, serotonergic, and alpha adrenergic receptors, or indomethacin to block the cyclooxygenase pathway of arachidonic acid metabolism, P-3 remained effective in enhancing contractile responses, even though these pretreatments altered the sensitivity and/or magnitude of contractions produced by substance P. When ETYA or NDGA were combined with indomethacin to also block the lipoxygenase pathway of arachidonic acid metabolism, the sensitizing effect of P-3 infection was diminished or abolished, especially at larger concentrations of substance P. With combination of FPL55712 and indomethacin, the sensitizing effect of P-3 was not abolished. Contractile responses to LTC4 and LTD4 were not enhanced by P-3 infection. The data suggest a selective influence of P-3 infection on the substance P system and provide evidence for a role of the lipoxygenase pathway of arachidonic acid metabolism in the sensitizing action. Peptide leukotrienes do not appear to be the lipoxygenase products involved in this effect of virus.

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