Store-operated calcium influx inhibits renin secretion

On the basis of evidence that changes in the extracellular concentration of calcium effectively modulate renin secretion from renal juxtaglomerular ce lls, our study aimed to determine the effect of calcium influx activated by depletion of intracellular calcium stores on renin secretion. For this pur pose we characterized the effects of the endoplasmatic Ca2+-ATPase inhibito rs thapsigargin (300 nM) and cyclopiazonic acid (20 mu M) on renin secretio n from isolated perfused rat kidneys. We found that Ca2+-ATPase inhibition caused a potent inhibition of basal renin secretion as well as renin secret ion activated by isoproterenol, bumetanide, and by a fall in the renal perf usion pressure. The inhibitory effect of Ca2+-ATPase inhibition on renin se cretion was reversed within seconds by lowering of the extracellular calciu m concentration into the submicromolar range but was not affected by lantha num, gadolinium, flufenamic acid, or amlodipine. These data suggest that ca lcium influx triggered by release of calcium from internal stores is a powe rful mechanism to inhibit renin secretion from juxtaglomerular cells. The s tore-triggered calcium influx pathway in juxtaglomerular cells is apparentl y not sensitive to classic blockers of the capacitative calcium entry pathw ay.