Abstract
PGD 2 is a major product of arachidonic acid metabolism by mast cells and is released in the lungs following allergen challenge. Activation of the classic PGD 2 receptor (DP receptor) results in stimulation of adenylyl cyclase, resulting in inhibition of platelet aggregation and smooth muscle relaxation. A second PGD 2 receptor has recently been identified and designated as the DP 2 receptor, or chemoattractant receptor-homologous molecule expressed on Th2 cells. PGD 2 acts through the DP 2 receptor to induce eosinophil chemotaxis, actin polymerization, calcium mobilization, and adhesion molecule expression. The most potent DP 2 receptor agonist yet identified is 15 R-methyl-PGD 2, which has the unnatural R configuration at C 15. 15-Deoxy- Δ 12,14-PGJ 2 is also a potent DP 2 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, PGD 2 may be an important proinflammatory mediator in asthma.
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