Role of PGE 2 in α 2 -induced inhibition of AVP- and cAMP-stimulated H 2 O, Na + , and urea transport in rat IMCD

• Published in: American journal of physiology. Renal physiology 2000-08, Vol.279 (2), p.F294-F301
• Main Authors: Rouch, Alexander J., Kudo, Lúcia H.
• Format: Article
• Language: English
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.2000.279.2.F294

PGE 2 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 α 2 -agonists also inhibit P f in the rat IMCD via post-cAMP-dependent events. The purpose of this study was to determine whether PGE 2 plays a role in α 2 -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 22 Na + 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 α 2 -agonists clonidine, oxymetazoline, and dexmedetomidine were used to test the role of PGE 2 in the α 2 -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 PGE 2 reduced these transport parameters. Indomethacin reversed α 2 inhibition of CPT-cAMP-stimulated P f , J lb , and P u , and subsequent addition of PGE 2 reduced transport in each case. Indomethacin partially reversed α 2 inhibition of AVP-stimulated P f , J lb , and P u , and PGE 2 reduced transport back to the α 2 -inhibited level. These results indicate that PGE 2 is a second messenger involved in the mechanism of transport inhibition mediated by α 2 -adrenoceptors via post-cAMP-dependent events in the rat IMCD.