P2Y2 receptor-stimulated release of prostaglandin E2 by rat inner medullary collecting duct preparations

Brett D. Welch, Noel G. Carlson, Huihui Shi, Leslie Myatt, Bellamkonda K. Kishore

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Extracellular nucleotides, acting through the P2Y2 receptor and the associated phosphoinositide-Ca2+ signaling pathway, inhibit AVP-stimulated osmotic water permeability in rat inner medullary collecting duct (IMCD). Because a rise in intracellular Ca2+ is frequently associated with enhanced arachidonic acid metabolism, we examined the effect of activation of the P2Y2 receptor on release of PGE2 in freshly prepared rat IMCD suspensions. Unstimulated IMCD released moderate, but significant, amounts of PGE2, which were more sensitive to cyclooxygenase (COX)-2 than COX-1 inhibition. Agonist activation of P2Y 2 receptor by adenosine 5′-O-(3-thiotriphosphate) enhanced release of PGE2 from IMCD in a time- and concentration-dependent fashion. Purinergic-stimulated release of PGE2 was completely blocked by nonspecific COX inhibitors (flurbiprofen and 2-acetoxyphenylhept-2-ynyl sulfide). Differential COX inhibition studies revealed that purinergic-stimulated release of PGE2 was more sensitive to a COX-1-specific inhibitor (valeroyl salicylate) than a COX-2-specific inhibitor (NS-398). Thus purinergic stimulation resulted in significantly more release of PGE2 in the presence of COX-2 inhibitor than COX-1 inhibitor. If it is assumed that increased release of PGE2 is related to its increased production, our results suggest that purinergic stimulation of IMCD results in enhanced production and release of PGE2 in a COX-1-dependent fashion. Because PGE2 is known to affect transport of water, salt, and urea in IMCD, interaction of the purinergic system with the prostanoid system in IMCD can modulate handling of water, salt, and urea by IMCD and, thus, may constitute an AVP-independent regulatory mechanism.

Original languageEnglish (US)
Pages (from-to)F711-F721
JournalAmerican Journal of Physiology - Renal Physiology
Volume285
Issue number4 54-4
StatePublished - Oct 1 2003

Keywords

  • Arachidonic acid
  • Arginine vasopressin
  • Cyclooxygenases
  • Extracellular nucleotides
  • Purinergic receptor

ASJC Scopus subject areas

  • Physiology
  • Urology

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