Cellular mechanisms of renin secretion.

Renin secretion from the juxtaglomerular cell is controlled by numerous receptors, humoral agents, and ions. Recently, a stretch receptor hypothesis has been advanced to suggest that all of these diverse factors control renin secretion by a mechanism initiated by a fall in cytoplasmic Ca2+. This fall in Ca2+ may be achieved by lowering Ca2+ influx, raising Ca2+ efflux, or sequestering Ca2+ into cellular organelles and binding sites. The increased renin secretion observed with low arterial pressure, beta-adrenergic agonists, parathyroid hormone, glucagon, cyclic AMP, prostaglandins, low Ca2+ and Ca2+ ionophore, high Mg2+, and Na+ and Cl- may be explained in this context. On the other hand, the decreased renin secretion observed with high pressure, alpha-adrenergic agonists, some prostaglandins, angiotensin, vasopressin, and high K+ may be explained by a rise in cytoplasmic Ca2+ mediated by an opposite sequence of events. Recent observations suggest that the fall in cytoplasmic Ca2+ sets in motion the transport of renin from its site of storage (granules) or synthesis into the cytoplasmic space and finally across the plasma membrane. Thus although renin is stored in granules, its secretion occurs by a process quite different from exocytosis.

Possible role of calmodulin in renin secretion from isolated rat kidneys and renal cells: studies with trifluoperazine.

Trifluoperazine, an inhibitor of calmodulin and calmodulin-directed secretion, was used to examine a possible role of calmodulin in renin secretion from isolated perfused kidneys and renal cortical cells. In isolated perfused kidneys trifluoperazine stimulated basal renin secretion in a dose-dependent manner, with 10 microM causing no stimulation and 50 microM causing 167% increase. Trifluoperazine potentiated the elevated renin secretion induced by isoprenaline and low Ca in isolated kidneys. In renal cortical cells trifluoperazine increased basal renin secretion and potentiated the secretion induced by Ca omission. Cells homogenized immediately after 1 h exposure to trifluoperazine had a substantial reduction in soluble renin without any effect on the change in granular renin. In the absence of trifluoperazine, soluble renin increased with O Ca and decreased with 1.5 mM-Ca. It is concluded that trifluoperazine stimulates renin secretion by a cellular mechanism possibly at the level of the juxtaglomerular cell. It is suggested that the role of trifluoperazine, and by inference calmodulin, in the secretion of renin may be quite different from its role in secretion of several other substances.