Regulation of Cyclooxygenase Activity in Airway Epithelium by Endogenous Nitric Oxide

Abstract

The role of nitric oxide (NO) in the activity of cyclooxygenase (COX) in cultured canine tracheal epithelium was studied. Tracheal epithelium spontaneously released prostaglandin E₂ (PGE₂), which is a product of COX. The release of PGE₂ was increased by bradykinin and was decreased by two NO synthase inhibitors: N^G-nitro-L-arginine methyl ester and N^G-monomethyl-L-arginine. That decrease was reversed in the presence of L-arginine. Chrolpromadin, but not aminoguanidine, inhibited PGE₂ production, which suggests that constitutive NO synthase is involved. Two stable NO donors, sodium nitroprusside and S-nitroso-N-acetyl DL-penicillamine, also increased the production of PGE₂. These effects were abolished by coincubation with hemoglobin, which binds and inactivates NO, but not by methylene blue, an inhibitor of soluble guanylate cyclase. NADPH diaphorase histochemistry of cultured tracheal cells revealed activity in the periphery of the cytoplasm. These results suggest that, in cultured canine tracheal epithelium, NO directly interacts with COX to regulate PGE₂ production.