Effects of osmolality and calcium on renin release from superfused rat glomeruli treated with nigericin or monensin.

Proton gradients may be important for the induction of swelling and exocytosis of secretory renin granules during basal renin release (RR). The sensitivity of renin release to changes in osmolality and to calcium was therefore tested on superfused rat glomeruli that had been pretreated with the monovalent cation/proton ionophores monensin and nigericin to dissipate granular proton gradients. Furthermore it was tested whether NH4Cl stimulates RR by inducing waterfluxes. Pretreatment of glomeruli with 10 microM nigericin or monensin inhibited RR, and suppressed the response to calcium removal, independently of the presence of 0.5 mM EGTA. In contrast, the stimulatory effect of a hypo-osmotic challenge (-20 mM sucrose) was unchanged after pretreatment with nigericin or monensin. The stimulation induced by 15 mM NH4Cl was prevented by addition of 20 mM sucrose. The results suggest that dissipation of proton gradients with the ionophores inhibit RR late in the secretory pathways, independently of effects on the Golgi-apparatus and intracellular calcium concentration. The results are consistent with the hypothesis that a low granular pH is important for driving JGC-granule swelling and exocytosis.