LUMINAL PROSTAGLANDIN-E RECEPTORS REGULATE SALT AND WATER TRANSPORT IN RABBIT CORTICAL COLLECTING DUCT

Prostaglandin E(2) (PGE(2)) is the major renal cyclooxygenase metabolite of arachidonic acid. Urinary excretion of PGE(2) is increased by dietary salt restriction, as well in cirrhosis and congestive heart failure. To determine whether urinary PGE(2) affects transport along the nephron, the actions of luminal PGE(2) were studied in the isolated perfused rabbit cortical collecting duct (CCD). Luminal PGE(2) transiently hyperpolarized transepithelial voltage (V-t) in a dose-dependent manner (half-maximal effect similar to 10(-8) M) in contrast to a sustained depolarization of V-t produced by basolateral PGE(2). Luminal PGE(2) (0.1 mu M) also significantly stimulated osmotic water permeability in the CCD. In CCDs cultured on semipermeable supports, apical PGE(2) stimulated adenosine 3',5'-cyclic monophosphate (cAMP) production, suggesting the effects of luminal PGE(2) are mediated by adenylyl cyclase-stimulating EP(2) or EP(4) receptors. Sulprostone, a PGE(2) analogue selective for EP(1) and EP(3) receptors, affected V-t only when applied from the basolateral but not the luminal surface. Luminal application of the EP(2) receptor agonist butaprost was also without effect. These results suggest that luminal PGE(2) affects V-t via a butaprost-insensitive EP(4) receptor. The V-t effect of luminal PGE(2) was not blocked by pertussis toxin, also arguing against an EP(3)-mediated G(i)-coupled effect. Finally, 1 mu M luminal PGE(2) only slightly increased CCD intracellular calcium concentration ([Ca2+](i)), in contrast to the marked increase in [Ca2+](i) produced by basolateral PGE(2) (0.1 mu M). These results suggest luminal EP(4) receptors stimulate cAMP generation in the CCD, thereby affecting water and ion transport. Urinary PGE(2) may importantly regulate salt and water transport in the collecting duct.