Structure-function analyses of eicosanoid receptors - Physiologic and therapeutic implications

Prostaglandins (PGs) are ubiquitous lipid mediators derived from cyclooxygenase (COX) metabolism of arachidonic acid that exert a broad range of physiologic activities including modulation of inflammation, ovulation, and arterial blood pressure. The physiologic actions of PGs are mediated in part by their interaction with specific G-protein-coupled PG receptors, Eight PG receptors have been cloned, including four for the major COX me tabolite, PGE(2). The physiologic roles of the PGE(2) receptors have been investigated utilizing subtype-selective agonists, localization of receptor mRNA expression, and creation of mire with targeted disruption of PG receptor genes, These analyses have delineated discrete roles for the various PG receptor subtypes, Recent studies on mice lacking the PGE(2) EP2 receptor have implicated the PGE(2) EP2 receptor subtype in arterial dilatation and salt-sensitive hypertension, and also Indicate that this receptor plays a key role in female fertility. The EP2 receptor may thus prove to be a productive target for pharmacological intervention in the treatment of hypertension and infertility.