EP(2) receptor mediates bronchodilation by PGE(2) in mice.
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).
Sheller
J R
JR
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA. James.Sheller@MCMail.Vanderbilt.edu
Mitchell
D
D
Meyrick
B
B
Oates
J
J
Breyer
R
R
D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001980:Bronchi / Q000187:drug effects; D016084:Bronchoconstriction / Q000187:drug effects; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D018078:Receptors, Prostaglandin E / Q000235:genetics / Q000502:physiology*; D058307:Receptors, Prostaglandin E, EP2 Subtype
D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; C545645:Ptger2 protein, mouse; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D016210:Methacholine Chloride; D015232:Dinoprostone