Luminal prostaglandin E receptors regulate salt and water transport in rabbit cortical collecting duct

Abstract

Prostaglandin E2 (PGE2) is the major renal cyclooxygenase metabolite of arachidonic acid. Urinary excretion of PGE2 is increased by dietary salt restriction, as well in cirrhosis and congestive heart failure. To determine whether urinary PGE2 affects transport along the nephron, the actions of luminal PGE2 were studied in the isolated perfused rabbit cortical collecting duct (CCD). Luminal PGE2 transiently hyperpolarized transepithelial voltage (Vt) in a dose-dependent manner (half-maximal effect approximately 10(-8) M) in contrast to a sustained depolarization of Vt produced by basolateral PGE2. Luminal PGE2 (0.1 microM) also significantly stimulated osmotic water permeability in the CCD. In CCDs cultured on semipermeable supports, apical PGE2 stimulated adenosine 3',5'-cyclic monophosphate (cAMP) production, suggesting the effects of luminal PGE2 are mediated by adenylyl cyclase-stimulating EP2 or EP4 receptors. Sulprostone, a PGE2 analogue selective for EP1 and EP3 receptors, affected Vt only when applied from the basolateral but not the luminal surface. Luminal application of the EP2 receptor agonist butaprost was also without effect. These results suggest that luminal PGE2 affects Vt via a butaprost-insensitive EP4 receptor. The Vt effect of luminal PGE2 was not blocked by pertussis toxin, also arguing against an EP3-mediated Gi-coupled effect. Finally, 1 microM luminal PGE2 only slightly increased CCD intracellular calcium concentration ([Ca2+]i), in contrast to the marked increase in [Ca2+]i produced by basolateral PGE2 (0.1 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Prostaglandin Signaling in the Renal Collecting Duct

“…Unpublished work from our laboratory indicates that PGT and COX-2 expression in Swiss 3T3 fibroblasts is coordinately regulated by serum. 4 Similarly, a recent report showed that PGT and COX-2 are coordinately regulated during the estrus cycle in the bovine corpus luteum (49). We propose that carrier-mediated PG reuptake represents a level of control that is complementary to the regulation of COX-2.…”

“…For example, cultured osteoblasts express both EP 1 and EP 4 receptors, which signal opposite effects on DNA synthesis and alkaline phosphatase activity (36). Similarly, the renal collecting duct expresses apical EP 4 receptors and basolateral EP 1 receptors that signal opposite effects on Na ϩ and water transport (4,5). Since PGE2 likely exits collecting duct cells non-directionally by simple diffusion (37,38), one method for directing PGE2 toward basolateral (EP 1 ) receptors would be to use an apical reuptake carrier like PGT.…”

“…On a smaller scale, the renal collecting expresses luminal EP 4 receptors, activation of which increases Na ϩ reabsorption and increases water reabsorption, and basolateral EP 1 receptors, activation of which signals the opposite effects (4,5). Clearly, to achieve the requisite fidelity in PGE2 signaling, rapid inactivation must occur.…”

Augmented cyclooxygenase-2 effects on renal function during varying states of angiotensin II

“…Another possible mechanism responsible for the reduced sodium excretion could involve COX-2-dependent sodium transport activity. Indeed, PGE 2 has been shown to reduce sodium transport in isolated thick ascending limbs (35) and collecting duct (33). Nevertheless, the absence of COX-2 effects during combined ACE inhibition could reflect diminished ANG II-dependent sodium reabsorption available for prostaglandin modulation that is otherwise present in the thick ascending limb or collecting duct or, indirectly, through aldosterone-regulated epithelial sodium channel activity (2,12).…”

“…The implication of dual prostaglandin sources on renal excretory function is highlighted by studies in cortical collecting ducts, where PGE 2 applied to the basolateral membrane decreases EP 1 or EP 3 receptor-mediated amiloride-sensitive sodium transport, whereas EP 4 receptor activation increases transport when applied apically (33). Furthermore, dietary sodium is positively correlated with apical expression of prostaglandin transporters (3).…”