Cloning and expression of the rabbit prostaglandin EP(4) receptor

Prostaglandin E(2) (PGE(2)) is an important regulator of systemic hemodynamics and epithelial ion transport. To further investigate the mechanism of PGE(2) action, a clone encoding a PGE(2) receptor was isolated from a rabbit kidney cortex cDNA library. Expression of the full-length cDNA in COS-1 cells yielded a ligand-binding profile typical for a butaprost-insensitive G(3)-coupled E-prostanoid (EP) receptor. Misoprostol-free acid, a receptor-selective PGE analogue, produced concentration-dependent increases in adenosine 3',5'-cyclic monophosphate production. The data are consistent with the receptor being an EP(4) subtype. Ribonuclease protection assays demonstrated that this receptor gene is highly expressed in intestine, uterus, and thymus, with lower but significant expression in kidney, whole adrenal, lung, spleen, and stomach. In situ hybridization in kidney revealed intense hybridization to glomeruli and urothelium of the renal pelvis. This prostanoid receptor was also highly expressed in the duodenal epithelium and adrenal cortex. The tissue distribution suggests a functional role for this receptor in mediating glomerular effects of PGE(2) and effects on aldosterone secretion, intestinal transport, and immune function.