PGD2

Prostaglandin D2 (PGD2) is a bioactive lipid mediator in the prostaglandin family. It is derived from arachidonic acid through the cyclooxygenase (COX) pathway and is produced by a variety of cells, most notably mast cells, but also including certain neurons and other tissues.

Biosynthesis of PGD2 involves conversion of arachidonic acid to prostaglandin H2 (PGH2) by COX-1 or COX-2, followed by the action of specific PGD synthases. There are two main PGD synthases in humans: lipocalin-type (L-PGDS) and hematopoietic-type (H-PGDS), which generate PGD2 in different cellular contexts and tissues.

PGD2 signals through two primary receptors: DP1 (PTGDR) and DP2 (CRTH2, GPR44). DP1 couples to Gs proteins, increasing cyclic AMP, while DP2 couples to Gi/o proteins, promoting calcium signaling and chemotaxis in immune cells. In the brain, PGD2 influences sleep regulation via DP1 signaling, contributing to sleep promotion.

Physiological and clinical roles of PGD2 include participation in allergic and inflammatory processes, particularly in mast cell–mediated responses in the airways and skin. It also contributes to vasodilation and, in the airways, can participate in bronchoconstriction under certain conditions. In addition to peripheral actions, PGD2 participates in central nervous system functions related to sleep and circadian biology.

Therapeutically, elevated PGD2 signaling is associated with allergic diseases such as asthma and rhinitis. DP2 antagonists have been investigated as potential treatments for these conditions. PGD2 is rapidly metabolized to various products, including 15-deoxy-Δ12,14-PGJ2, contributing to its short in vivo half-life.