Steppan, D. and Pan, L. and Gross, K. W. and Kurtz, A. (2018) Analysis of the calcium paradox of renin secretion. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 315 (4). F834-F843. ISSN 1931-857X, 1522-1466
Full text not available from this repository. (Request a copy)Abstract
The secretion of the protease renin from renal juxtaglomerular cells is enhanced by subnormal extracellular calcium concentrations. The mechanisms underlying this atypical effect of calcium have not yet been unraveled. We therefore aimed to characterize the effect of extracellular calcium concentration on calcium handling of juxtaglomerular cells and on renin secretion in more detail. For this purpose, we used a combination of experiments with isolated perfused mouse kidneys and direct calcium measurements in renin-secreting cells in situ. We found that lowering of the extracellular calcium concentration led to a sustained elevation of renin secretion. Electron-microscopical analysis of renin-secreting cells exposed to subnormal extracellular calcium concentrations revealed big omega-shaped structures resulting from the intracellular fusion and subsequent emptying of renin storage vesicles. The calcium concentration dependencies as well as the kinetics of changes were rather similar for renin secretion and for renovascular resistance. Since vascular resistance is fundamentally influenced by myosin light chain kinase (MLCK), myosin light chain phosphatase (MLCP), and Rho-associated protein kinase (Rho-K) activities, we examined the effects of MLCK-, MLCP-, and Rho-K inhibitors on renin secretion. Only MLCK inhibition stimulated renin secretion. Conversely, inhibition of MCLP activity lowered perfusate flow and strongly inhibited renin secretion, which could not be reversed by lowering of the extracellular calcium concentration. Renin-secreting cells and smooth muscle cells of afferent arterioles showed immunoreactivity of MLCK. These findings suggest that the inhibitory effect of calcium on renin secretion could be explained by phosphorylation-dependent processes under control of the MLCK.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LIGHT-CHAIN KINASE; PERFUSED RAT KIDNEYS; ISOLATED JUXTAGLOMERULAR CELLS; SMOOTH-MUSCLE; COMPOUND EXOCYTOSIS; CHANNEL AGONIST; CYCLIC-AMP; DIFFERENTIAL REGULATION; INTRACELLULAR CALCIUM; NEUROENDOCRINE CELLS; calcium; MLCK; renin |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Dec 2019 14:54 |
| Last Modified: | 09 Dec 2019 14:54 |
| URI: | https://pred.uni-regensburg.de/id/eprint/13765 |
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