EP2 receptor mediates bronchodilation by PGE(2) in mice

PGE(2) is an important cyclooxygenase product that modulates airway inflamm atory and smooth muscle responses. Signal transduction is mediated by four EP receptor subtypes that cause distinct effects on cell metabolism. To det ermine the role of EP2 receptor activation, we produced a mouse lacking the EP2 receptor by targeted gene disruption. The effect of aerosolized PGE(2) and other agonists was measured using barometric plethysmography and by me asurements of lung resistance in mechanically ventilated mice. lnhalation o f PGE(2) inhibited methacholine responses in wild-type but not in mice lack ing the EP2 receptor [EP2(-/-)]. After airway constriction was induced by m ethacholine 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 EP2(-/-) mice (from 0.73 +/- 0.08 to 1.27 +/- 0.19). Similar results were obtained in mechanically ventilated mice. These data indicate that the EP2 receptor mediates the bronchodilation effect of PGE(2).