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.
Ohbayashi
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Internal Medicine II, Nagoya University School of Medicine, 65 Tsuruma-cho, Showa-ku, 466-8550, Nagoya, Japan. ohbayasi@nn.iij4.u.or.jp
Yamaki
K I
KI
D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016084:Bronchoconstriction / Q000187:drug effects*; D002199:Capillary Permeability / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005070:Evans Blue; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D017997:Leukotriene C4 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D045265:Natriuretic Peptides; D010455:Peptides / Q000008:administration & dosage* / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000502:physiology; D014132:Trachea / Q000187:drug effects
D045265:Natriuretic Peptides; D010455:Peptides; C084362:uroguanylin; D017997:Leukotriene C4; D005070:Evans Blue