P2Y2 receptor-mediated release of prostaglandin E2 by IMCD is altered in hydrated and dehydrated rats: relevance to AVP-independent regulation of IMCD function.
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Sun R, Carlson NG, Hemmert AC, Kishore BK
P2Y2 receptor-mediated release of prostaglandin E2 by IMCD is altered in hydrated and dehydrated rats: relevance to AVP-independent regulation of IMCD function.
Am J Physiol Renal Physiol. 2005 Sep;289(3):F585-92. Epub 2005 Apr 19.
- PubMed ID
- 15840771 [ View in PubMed]
- Abstract
Circulating vasopressin levels change in hydrated and dehydrated conditions and thus control osmotic water permeability (P(f)) of the inner medullary collecting duct (IMCD). Prostaglandin E2 (PGE2) antagonizes vasopressin-induced P(f) of IMCD. Previously, we showed that activation of P2Y2 receptor (P2Y2-R) in IMCD results in production and release of PGE2, and P2Y2-R mRNA and protein are significantly elevated in inner medullas of hydrated rats compared with dehydrated rats. Therefore, we examined whether the altered expression of P2Y2-R in hydrated and dehydrated states is associated with corresponding changes in P2Y2-R-mediated PGE2 release by the IMCD. Rats were hydrated by providing sucrose water as the sole drinking fluid or dehydrated by water deprivation for 2 days. This resulted in high output-low osmolality and low output-high osmolality urines in hydrated and dehydrated rats, respectively. In hydrated rats, there was a significant increase in tubular fluid PGE2, measured indirectly by assessing the urinary PGE2 metabolite. Stimulation of freshly isolated IMCD preparations in vitro with P2Y2-R agonist (ATPgammaS) showed a marked increase in the release of PGE2 in hydrated rats compared with normal rats. These responses were blunted in the IMCD prepared from dehydrated rats. The P2Y2-R-mediated PGE2 release in the IMCD of hydrated rats was mediated largely by cyclooxygenase (COX)-1 as COX-1-specific inhibitor valeroyl salicylate completely blocked the release. The COX-2-specific inhibitor N5398 had only a modest and insignificant inhibitory effect. In conclusion, the increased sensitivity of purinergic-prostanoid interaction seen in the IMCD of hydrated rats may represent a novel vasopressin-independent regulatory mechanism of IMCD function.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Magnesium salicylate Prostaglandin G/H synthase 1 Protein Humans YesInhibitorDetails Salicylic acid Prostaglandin G/H synthase 1 Protein Humans YesInhibitorDetails