Role of PGE2 in α2-induced inhibition of AVP- and cAMP-stimulated H2O, Na+, and urea transport in rat IMCD

Abstract

PGE2 inhibits osmotic water permeability ( P f) in the rat inner medullary collecting duct (IMCD) via cellular events occurring after the stimulation of cAMP, i.e., post-cAMP-dependent events. The α2-agonists also inhibit P f in the rat IMCD via post-cAMP-dependent events. The purpose of this study was to determine whether PGE2 plays a role in α2-mediated inhibition of P f, Na+, and urea transport in the rat IMCD. Isolated terminal IMCDs from Wistar rats were perfused to measure, in separate experiments, P f, lumen-to-bath22Na+ transport ( J lb), and urea permeability ( P u). Transport was stimulated with 220 pM arginine vasopressin (AVP) or 0.1 mM 8-(4-chlorophenylthio)-cAMP (CPT-cAMP). Indomethacin was used to inhibit endogenous prostaglandin synthesis, and the α2-agonists clonidine, oxymetazoline, and dexmedetomidine were used to test the role of PGE2 in the α2-mediated mechanism that inhibits transport. All agents were added to the bath. Indomethacin at 5 μM significantly elevated CPT-cAMP-stimulated P f, J lb, and P u, and subsequent addition of 100 nM PGE2 reduced these transport parameters. Indomethacin reversed α2 inhibition of CPT-cAMP-stimulated P f, J lb, and P u, and subsequent addition of PGE2 reduced transport in each case. Indomethacin partially reversed α2 inhibition of AVP-stimulated P f, J lb, and P u, and PGE2 reduced transport back to the α2-inhibited level. These results indicate that PGE2 is a second messenger involved in the mechanism of transport inhibition mediated by α2-adrenoceptors via post-cAMP-dependent events in the rat IMCD.