Effect of UUO on D1aR expression reveals a link among dopamine, transforming growth factor-β, and nitric oxide

Joshua M. Stern, Jie Chen, Randi B. Silver, Dix P. Poppas, E. Darracott Vaughan, Diane Felsen

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Interactions between transforming growth factor-β (TGF-β) and nitric oxide (NO) are important in the pathophysiology of unilateral ureteral obstruction (UUO). Dopamine (DA) is a vasoactive renal mediator active at the D1A receptor (D1AR), which has not been studied in UUO; therefore, we examined the interactions among DA, TGF-β, and NO in UUO. In vivo, UUO was carried out in rats with or without concurrent treatment with 1D11, a monoclonal antibody to TGF-β, for 14 days. In vitro, NRK-52E cells (normal rat kidney tubules) were treated with DA, and NO and TGF-β release were examined. UUO. resulted in a 70% decrease in the expression of renal D 1AR, confirmed by both Western blot analysis and immunohistochemistry. 1D11 treatment restored expression to 60% of control values. DA treatment decreased NRK-52E release of TGF-β by 80%; conversely, DA significantly increased NO release from NRK-52E cells. These results suggest that DA modulates the release of cytokines, which are involved in the fibrotic and apoptotic sequelae of UUO, and that these effects are independent of DA's known vasoactive properties.

Original languageEnglish (US)
Pages (from-to)F509-F515
JournalAmerican Journal of Physiology - Renal Physiology
Volume286
Issue number3 55-3
StatePublished - Mar 1 2004
Externally publishedYes

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Keywords

  • Apoptosis
  • D receptor
  • Kidney
  • Obstructive uropathy
  • Unilateral ureteral obstruction

ASJC Scopus subject areas

  • Physiology
  • Urology

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