Regulation of renin release via cyclic adp-ribose-mediated signaling: Evidence from mice lacking CD38 gene

Jing Xiong, Min Xia, Fan Yi, Justine M. Abais, Ningjun Li, Krishna M. Boini, Pin Lan Li

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Background/Aims: Despite extensive studies, the intracellular regulatory mechanism of renin production and release is still poorly understood. The present study was designed to test whether CD38-ADP-ribosylcyclase signaling pathway contributes to the regulation of renin production and release, and to examine whether CD38 gene knockout (CD38 -/- ) can change this important renal endocrinal function. Methods: ADP-ribosylcyclase activity was estimated utilizing HPLC, cADPR levels from western blot, plasma renin activity from RIA kit, urinary sodium and potassium excretion from fame photometry. Results: The expression of CD38 and the activity of ADP-ribosylcyclase to produce cyclic ADP-ribose (cADPR) were nearly abolished in the kidney from CD38 -/- mice, indicating that CD38 gene is a major enzyme responsible for the generation of cADPR in vivo. Mice lacking CD38 gene showed increased plasma renin activity (PRA) in either conscious or anesthetized status (P<0.05). Low salt intake significantly increased, but high salt intake significantly decreased renin release in both CD38 +/+ and CD38 -/- mice. In acute experiments, it was demonstrated that plasma renin activity (PRA) significantly increased upon isoprenaline infusion in CD38 -/- mice compared to CD38 +/+ mice. Accompanied with such increase in PRA, glomerular filtration rate (GFR), renal blood flow (RBF), urine volume (UV) and sodium excretion (U Na V) more significantly decreased in CD38 -/- than CD38 +/+ mice. Similarly, more increases in PRA but more decreases in GFR, RBF, UV and U Na V were observed in CD38 -/- than CD38 +/+ mice when they had a low renal perfusion pressure (RPP). Conclusion: CD38-cADPR-mediated signaling may importantly contribute to the maintenance of low PRA and participate in the regulation of renal hemodynamics and excretory function in mice.

Original languageEnglish (US)
Pages (from-to)44-55
Number of pages12
JournalCellular Physiology and Biochemistry
Volume31
Issue number1
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

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Keywords

  • ADP-ribosylcyclase
  • Juxtaglomerular apparatus
  • Renal hemodynamics
  • Renin angiotensin II system

ASJC Scopus subject areas

  • Physiology

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