A novel PGD2 receptor expressed in eosinophils

Abstract

PGD₂ is a major product of arachidonic acid metabolism by mast cells and is released in the lungs following allergen challenge. Activation of the classic PGD₂ receptor (DP receptor) results in stimulation of adenylyl cyclase, resulting in inhibition of platelet aggregation and smooth muscle relaxation. A second PGD₂ receptor has recently been identified and designated as the DP₂ receptor, or chemoattractant receptor-homologous molecule expressed on Th2 cells. PGD₂ acts through the DP₂ receptor to induce eosinophil chemotaxis, actin polymerization, calcium mobilization, and adhesion molecule expression. The most potent DP₂ receptor agonist yet identified is 15R-methyl-PGD₂, which has the unnatural R configuration at C₁₅. 15-Deoxy-Δ^12,14-PGJ₂ is also a potent DP₂ receptor agonist that activates eosinophils at concentrations much lower than those required for its anti-inflammatory effects. Because of its critical location in the lung and its potent effects on eosinophils, PGD₂ may be an important proinflammatory mediator in asthma.