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EP 2 receptor mediates bronchodilation by PGE 2 in mice

2000; American Physiological Society; Volume: 88; Issue: 6 Linguagem: Inglês

10.1152/jappl.2000.88.6.2214

8750-7587

James R. Sheller, Daphne B. Mitchell, Barbara Meyrick, John Oates, Richard Breyer,

Respiratory and Cough-Related Research

PGE 2 is an important cyclooxygenase product that modulates airway inflammatory and smooth muscle responses. Signal transduction is mediated by four EP receptor subtypes that cause distinct effects on cell metabolism. To determine the role of EP 2 receptor activation, we produced a mouse lacking the EP 2 receptor by targeted gene disruption. The effect of aerosolized PGE 2 and other agonists was measured using barometric plethysmography and by measurements of lung resistance in mechanically ventilated mice. Inhalation of PGE 2 inhibited methacholine responses in wild-type but not in mice lacking the EP 2 receptor [EP 2 (−/−)]. After airway constriction was induced by methacholine aerosol, PGE 2 reduced the airway constriction enhanced pause in wild-type mice (from 0.88 ± 0.15 to 0.55 ± 0.06) but increased it in EP 2 (−/−) mice (from 0.73 ± 0.08 to 1.27 ± 0.19). Similar results were obtained in mechanically ventilated mice. These data indicate that the EP 2 receptor mediates the bronchodilation effect of PGE 2 .