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

• Main Authors: Jing Xiong, Min Xia, Fan Yi, Justine M. Abais, Ningjun Li, Krishna M. Boini, Pin-Lan Li
• Format: Article
• Language: English
• Published: Cell Physiol Biochem Press GmbH & Co KG 2013-01-01
• Series: Cellular Physiology and Biochemistry
• Subjects: ADP-ribosylcyclase; Ca2+ signaling; Renin angiotensin II system; Renal hemodynamics; Juxtaglomerular apparatus
• Online Access: http://www.karger.com/Article/FullText/343348

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+/+ 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 (UNaV) more significantly decreased in CD38-/- than CD38+/+ mice. Similarly, more increases in PRA but more decreases in GFR, RBF, UV and UNaV 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.