EP2 receptor mediates bronchodilation by PGE2 in mice

Abstract

PGE2 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 EP2 receptor activation, we produced a mouse lacking the EP2 receptor by targeted gene disruption. The effect of aerosolized PGE2 and other agonists was measured using barometric plethysmography and by measurements of lung resistance in mechanically ventilated mice. Inhalation of PGE2 inhibited methacholine responses in wild-type but not in mice lacking the EP2 receptor [EP2(−/−)]. After airway constriction was induced by methacholine aerosol, PGE2reduced 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 PGE2.