title: P2Y2 receptor-stimulated release of prostaglandin E2 by rat inner medullary collecting duct preparations.
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 P2Y2 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.
authors.affiliation: Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City 84132, USA.
authors.forename: Brett D
authors.initials: BD
authors.lastname: Welch
authors.forename: Noel G
authors.initials: NG
authors.lastname: Carlson
authors.forename: Huihui
authors.initials: H
authors.lastname: Shi
authors.forename: Leslie
authors.initials: L
authors.lastname: Myatt
authors.forename: Bellamkonda K
authors.initials: BK
authors.lastname: Kishore
mesh_terms: D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002469:Cell Separation / Q000379:methods; D002470:Cell Survival; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007679:Kidney Medulla; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008565:Membrane Proteins; D009994:Osmolar Concentration; D010741:Phospholipases A / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases; D058910:Purinergic P2 Receptor Agonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D058473:Receptors, Purinergic P2Y2
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; C546387:P2ry2 protein, rat; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; C022571:adenosine 5'-O-(3-thiotriphosphate); D000255:Adenosine Triphosphate; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D010741:Phospholipases A; D015232:Dinoprostone