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

Alexander J. Rouch, Lúcia H. Kudo

Research output: Contribution to journalArticle

31 Scopus citations

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-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.

Original languageEnglish
Pages (from-to)F294-F301
JournalAmerican Journal of Physiology - Renal Physiology
Volume279
Issue number2 48-2
StatePublished - 18 Sep 2000

Keywords

  • Inner medullary collecting duct
  • Osmotic water permeability
  • Second messengers
  • Signaling pathways
  • α-adrenoceptor

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