FUNCTIONAL AND MOLECULAR ASPECTS OF RENAL PROSTAGLANDIN RECEPTORS

The diverse intrarenal effects of the prostaglandins (PG) are mediated by distinct guanine nucleotide regulatory protein (G-protein)-coupled receptors. The cDNA for these receptors have been cloned, their signa l transduction mechanisms determined, and their intrarenal distributio n mapped. PGE(2), the major intrarenal prostaglandin, interacts with a t least three distinct E-prostanoid (EP) receptors that are highly exp ressed in specific regions of the kidney. Each EP receptor not only se lectively binds PGE(2), but also preferentially couples to different s ignal transduction pathways, including: stimulation of cAMP generation , via G(q) (EP(2) and EP(4) receptors); inhibition of cAMP generation, via G(i) (EP(3) receptors); and activation of phosphatidylinositol hy drolysis (EP(1) receptor), via one of the Gq family members. Activatio n of each these EP receptors is responsible for a distinct renal effec t of PGE(2), including its well-described renal hemodynamic and transp ort effects along the nephron. Other intrarenal prostanoid receptors i nclude the PGF(2 alpha) receptor (FP), the thromboxane A(2) receptor ( TP) and the prostacyclin receptor (IP). Knowledge about localization o f these receptors and their affinities for receptor-selective agonists and antagonists should aid in the understanding of renal disease and the development of therapeutic strategies for the use of these prostag landin analogs in select renal diseases.