mPGES-1 deletion potentiates urine concentrating capability after water deprivation

Zhanjun Jia, Gang Liu, Maicy Downton, Zheng Dong, Aihua Zhang, Tianxin Yang

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

PGE 2 plays an important role in the regulation of fluid metabolism chiefly via antagonizing vasopressin-induced osmotic permeability in the distal nephron, but its enzymatic sources remain uncertain. The present study was undertaken to investigate the potential role of microsomal PGE synthase (mPGES)-1 in the regulation of urine concentrating ability after water deprivation (WD). Following 24-h WD, wild-type (WT) mice exhibited a significant reduction in urine volume, accompanied by a significant elevation in urine osmolality compared with control groups. In contrast, in response to WD, mPGES-1 knockout (KO) mice had much less urine volume and higher urine osmolality. Analysis of plasma volume by measurement of hematocrit and by using a nanoparticle-based method consistently demonstrated that dehydrated WT mice were volume depleted, which was significantly improved in the KO mice. WD induced a twofold increase in urinary PGE 2 output in WT mice, which was completely blocked by mPGES-1 deletion. At baseline, the KO mice had a 20% increase in V 2 receptor mRNA expression in the renal medulla but not the cortex compared with WT controls; the expression was unaffected by WD irrespective of the genotype. In response to WD, renal medullary aquaporin-2 (AQP2) mRNA exhibited a 60% increase in WT mice, and this increase was greater in the KO mice. Immunoblotting demonstrated increased renal medullary AQP2 protein abundance in both genotypes following WD, with a greater increase in the KO mice. Similar results were obtained by using immunohistochemistry. Paradoxically, plasma AVP response to WD seen in WT mice was absent in the KO mice. Taken together, these results suggest that mPGES-1-derived PGE 2 reduces urine concentrating ability through suppression of renal medullary expression of V 2 receptors and AQP2 but may enhance it by mediating the central AVP response.

Original languageEnglish (US)
Pages (from-to)F1005-F1012
JournalAmerican Journal of Physiology - Renal Physiology
Volume302
Issue number8
DOIs
StatePublished - Apr 15 2012

Keywords

  • Aquaporin-2
  • PGE
  • Vasopressin

ASJC Scopus subject areas

  • Physiology
  • Urology

Fingerprint Dive into the research topics of 'mPGES-1 deletion potentiates urine concentrating capability after water deprivation'. Together they form a unique fingerprint.

  • Cite this