Effects of amines, monensin and nigericin on the renin release from isolated superfused rat glomeruli

Renin release (RR) in vitro has been shown to depend upon exocytosis, which is brought about by osmotically induced swelling of the acidic secretory granules. Since granule acidity has been suggested to be responsible for the exocytosis of other secretory granules (the chemiosmotic hypothesis), experiments were designed to test its possible significance in the RR from isolated superfused rat glomeruli. Each experiment comprised 5-6 series each of 14 consecutive 12 min periods. Changes in the extracellular pH from 7.4 to 7.8 by an increase in the concentration of bicarbonate inhibited the RR transiently. Alkalinization of the cell interior was achieved with weak permeable bases and ionophores. At low concentrations (5 mM NH4Cl; 0.2 mM chloroquine) the weak bases caused a delayed inhibition of the RR, while at higher concentrations (15 and 30 mM NH4Cl; 10 mM methylamine) the inhibitory effect was overlaid with a transient stimulation. 1.5 mM NH4Cl and 10 and 20 microM chloroquine had no effect. Addition of 10 microM of the Na-H ionophore monensin also caused a transient stimulation followed by a progressive inhibition. 0.1 microM monensin had no effect. The above procedures cause increases in both the granular and the cytosolic pH. The K-H ionophore nigericin will cause an increase in the granular pH but a decrease in the cytosolic pH because of the prevailing ionic gradients. Since the effect of 10 microM nigericin was similar to that of monensin, it is concluded that the above effects are due to the increase in the intragranular pH. Thus, the maintenance of a low intragranular pH is of importance for a continuous RR.(ABSTRACT TRUNCATED AT 250 WORDS)