Mechanisms of ionophore-induced stimulation of renin secretion with special reference to a chemiosmotic hypothesis

Abstract

The effects of several ionophores on renin secretion were investigated in rabbit renal cortical slices. When slices were incubated in the absence of Ca++, the K+ ionophore valinomycin (10(-5) approximately 5 x 10(-4) M) or the monovalent cation ionophore nonactin (10(-4) M) stimulated renin secretion about 2-fold. The renin secretion stimulated by valinomycin was further increased by inclusion of the H+ ionophore, carbonylcyanide m-chlorophenylhydrazone. The electroneutral K+/H+ exchange ionophore nigericin (10(-5) approximately 5 x 10(-4) M) stimulated renin secretion in a dose-dependent manner, producing a maximal stimulation of about 17-fold. Another electroneutral exchange ionophore, monensin, also significantly stimulated secretion. The stimulation by both valinomycin and nigericin was apparent whether slices were incubated in Na(+)-rich or K(+)-rich media. The extent of stimulation by the two ionophores was dependent upon the presence of anion with acetate greater than Cl greater than isethionate greater than thiocyanate. Thiocyanate itself markedly inhibited renin secretion. Incubating of slices in an iso-osmotic ammonium acetate medium which is known to induce rapid swelling of secretory granules, stimulated renin secretion to the magnitude comparable to that of maximal stimulation by nigericin in a potassium acetate medium. The pattern of response to these ionophores indicates that changes in K+, H+ and anion gradients across the renin secretory granule may modulate renin secretory rate. It is proposed that conditions which allow accumulation of K+ and anion within acidic renin secretory granules lead to osmotic swelling of the granules and that granule swelling may promote exocytosis.