FUNCTIONAL AND MOLECULAR ASPECTS OF PROSTAGLANDIN-E RECEPTORS IN THE CORTICAL COLLECTING DUCT

Endogenous prostaglandin (PG) E(2) production potently modulates salt and water transport in the kidney. Multiple direct effects of PGE(2) on epithelial water and sodium transport have been demonstrated in the rabbit cortical collecting duct (CCD). Both functional and molecular studies now suggest that these disparate effects of PGE(2) on CCD function are mediated by different EP receptors. When added in the presence of vasopressin, PGE(2) inhibits cyclic AMP generation and water absorption. These effects are mediated via an inhibitory G-protein (G(1)). In situ hybridization demonstrates high levels of expression of the G(1)-coupled EP(3) receptor in the rabbit collecting duct. However, by itself, PGE(2) also stimulates cyclic AMP generation and water permeability, These effects appear to be mediated via a distinct EP receptor (possibly an EP(4) receptor). PGE(2) also increases intracellular Ca2+ in the CCD and inhibits Na+ absorption via a Ca2+-dependent mechanism. The EP(1) receptor is postulated to be responsible for this action of PGE(2). We suggest receptor-selective prostaglandin analogs may be used to selectively modulate sodium and water transport in the kidney.