Substance P relaxes rat bronchial smooth muscle via epithelial prostanoid synthesis

Background: Substance P is present in bronchial nerve fibres, The physiolog ical actions of substance P are mediated via tachykinin NK1 receptors, Immu nochemical studies have demonstrated tachykinin NK1 receptors in the rat ai rway epithelium, Objective: To elucidate how epithelial tachykinin NK1 rece ptors affect smooth muscle response to substance P. Methods: Contractile re sponse of isolated rat bronchial trunk with or without epithelium was recor ded. Results: In intact segments precontracted by 5-hydroxytryptamine, rela xation was induced by substance P and the nitric oxide donor, sodium nitrop russide, Removal of the epithelium abolished relaxation induced by substanc e P but did not affect relaxation induced by sodium nitroprusside. The cycl o-oxygenase inhibitor, indomethacin, but not the nitric oxide synthase inhi bitor, L-N-G-monomethylarginine, reduced the relaxation in response to subs tance P, Conclusions: Epithelial tachykinin NK1 receptors mediate substance -P-induced relaxation of rat bronchial smooth muscle via release of prostan oids but not nitric oxide.