Calcium-dependent inhibitory step in control of renin secretion

The regulatory step for Ca(2+)- and calmodulin-dependent control of renin secretion was studied in rabbit renal cortical slices. Renin secretion was stimulated by adding the K(+)-H+ exchange ionophore nigericin or a weak base, benzylamine, to Ca(2+)-free incubation medium. Both nigericin and benzylamine can produce chemiosmotic swelling of acidic intracellular organelles in a pH gradient-dependent manner. Swelling of renin secretory granules may account for the stimulatory effects of these two agents on renin secretion. The stimulation of renin secretion by each of these agents was prevented by including Ca2+ in the incubation medium. The inhibitory effects of Ca2+ were reversed by the calmodulin antagonist calmidazolium, suggesting that the Ca2+ inhibition may be mediated by calmodulin. However, when renin secretion was first stimulated by nigericin or benzylamine in Ca(2+)-free medium, subsequent addition of Ca2+ to the incubation medium failed to reverse the stimulation. These results therefore suggest that Ca2+ acting through calmodulin may exert its inhibitory effects on renin secretion by blocking an early step in the cellular events that lead to renin secretion such as pH gradient-dependent swelling of renin secretory granule.