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 cells, our study aimed to determine the effect of calcium influx activated by depletion of intracellular calcium stores on renin secretion. For this purpose we characterized the effects of the endoplasmatic Ca(2+)-ATPase inhibitors thapsigargin (300 nM) and cyclopiazonic acid (20 microM) on renin secretion from isolated perfused rat kidneys. We found that Ca(2+)-ATPase inhibition caused a potent inhibition of basal renin secretion as well as renin secretion activated by isoproterenol, bumetanide, and by a fall in the renal perfusion pressure. The inhibitory effect of Ca(2+)-ATPase inhibition on renin secretion was reversed within seconds by lowering of the extracellular calcium concentration into the submicromolar range but was not affected by lanthanum, gadolinium, flufenamic acid, or amlodipine. These data suggest that calcium influx triggered by release of calcium from internal stores is a powerful mechanism to inhibit renin secretion from juxtaglomerular cells. The store-triggered calcium influx pathway in juxtaglomerular cells is apparently not sensitive to classic blockers of the capacitative calcium entry pathway.
Schweda
F
F
Institut für Physiologie I, Universität Regensburg, D-93040 Regensburg, Germany. frank.schweda@klinik.uniregensburg.de
Riegger
G A
GA
Kurtz
A
A
Krämer
B K
BK
D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004232:Diuretics / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007606:Juxtaglomerular Apparatus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D007700:Kinetics; D008297:Male; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000378:metabolism*; D019284:Thapsigargin / Q000037:antagonists & inhibitors / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004232:Diuretics; D004791:Enzyme Inhibitors; D007211:Indoles; D002034:Bumetanide; D004533:Egtazic Acid; D019284:Thapsigargin; D012083:Renin; D000252:Calcium-Transporting ATPases; D007545:Isoproterenol; D002118:Calcium; C000543:cyclopiazonic acid