Both inhalant and intravenous uroguanylin inhibit leukotriene C4-induced airway changes.

Uroguanylin, a well-known ligand of guanylyl cyclase C receptor in the gastrointestinal tissue, has recently been reported to have pulmonary effects. We investigated the inhibitory effects of uroguanylin against leukotriene C4-induced bronchoconstriction and airway microvascular leakage. Anesthetized guinea pigs, ventilated via a tracheal cannula in a plethysmograph box, were measured by pulmonary mechanics for 10 min after i.v. administering 2 microg/kg leukotriene C4. Airway microvascular leakage was assessed by extravasation of Evans blue dye into airway tissues. Both inhalant and i.v. pretreatment of uroguanylin significantly inhibited leukotriene C4-induced pulmonary changes in a dose-dependent manner, suggesting its effectiveness against an asthmatic condition.