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

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-bath ²²Na⁺ 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.