Regulation of Renin Release via Cyclic ADP-Ribose-Mediated Signaling: Evidence from Mice Lacking CD38 Gene

Department of Pharmacology & Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA.
Cellular Physiology and Biochemistry (Impact Factor: 3.55). 01/2013; 31(1):44-55. DOI: 10.1159/000343348
Source: PubMed

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.


Available from: Jing Xiong, Sep 16, 2014
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