| Abstrakt: |
PGE2inhibits osmotic water permeability (Pf) 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 Pfin the rat IMCD via post-cAMP-dependent events. The purpose of this study was to determine whether PGE2plays a role in α2-mediated inhibition of Pf, Na+, and urea transport in the rat IMCD. Isolated terminal IMCDs from Wistar rats were perfused to measure, in separate experiments, Pf, lumen-to-bath22Na+transport (Jlb), and urea permeability (Pu). 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 PGE2in the α2-mediated mechanism that inhibits transport. All agents were added to the bath. Indomethacin at 5 μM significantly elevated CPT-cAMP-stimulated Pf,Jlb, and Pu, and subsequent addition of 100 nM PGE2reduced these transport parameters. Indomethacin reversed α2inhibition of CPT-cAMP-stimulated Pf,Jlb, and Pu, and subsequent addition of PGE2reduced transport in each case. Indomethacin partially reversed α2inhibition of AVP-stimulated Pf, Jlb, and Pu, and PGE2reduced transport back to the α2-inhibited level. These results indicate that PGE2is a second messenger involved in the mechanism of transport inhibition mediated by α2-adrenoceptors via post-cAMP-dependent events in the rat IMCD. |
