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

Prostaglandin E(2) (PGE(2)) is the major renal cyclooxygenase metaboli te of arachidonic acid. Urinary excretion of PGE(2) is increased by di etary salt restriction, as well in cirrhosis and congestive heart fail ure. To determine whether urinary PGE(2) affects transport along the n ephron, the actions of luminal PGE(2) were studied in the isolated per fused rabbit cortical collecting duct (CCD). Luminal PGE(2) transientl y hyperpolarized transepithelial voltage (V-t) in a dose-dependent man ner (half-maximal effect similar to 10(-8) M) in contrast to a sustain ed 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, sug gesting 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 applie d from the basolateral but not the luminal surface. Luminal applicatio n of the EP(2) receptor agonist butaprost was also without effect. The se results suggest that luminal PGE(2) affects V-t via a butaprost-ins ensitive EP(4) receptor. The V-t effect of luminal PGE(2) was not bloc ked by pertussis toxin, also arguing against an EP(3)-mediated G(i)-co upled effect. Finally, 1 mu M luminal PGE(2) only slightly increased C CD 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 genera tion in the CCD, thereby affecting water and ion transport. Urinary PG E(2) may importantly regulate salt and water transport in the collecti ng duct.