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

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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
DOIs
StatePublished - 2000

Keywords

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

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