Stimulation of renin secretion by non-diuretic sulfhydryl reagents

Organomercurial diuretics stimulate renin secretion although the underlying cellular mechanisms remain undefined. Since organomercurials are also known to react with sulfhydryl groups, the present studies determined the effects of sulfhydryl reagents on renin secretion. The effects of the non-diuretic mercurial agent, parachloromercuriphenyl-sulfonate (PCMPS), as well as that of other sulfhydryl reagents, N-ethylmaleimide (NEM), N-phenylmaleimide (NPM) and monobromotrimethylammoniobimane (qBBR), on renin secretion were determined in rabbit renal cortical slices. All four reagents stimulated renin secretion. NEM, which has a high membrane permeability, stimulated secretion to a relatively small extent and its effects were not apparent for at least one hour. Conversely, PCMPS, which is much less permanent than NEM, produced the largest stimulation and these effects were apparent within one hour. The stimulation of secretion by sulfhydryl reagents was independent of the concentration of Ca2+, Na+, and K+ in the incubation media, suggesting that the stimulation is not secondary to alterations of intracellular ion concentrations. These results raise the possibility of direct involvement of sulfhydryl groups of particular membrane protein(s) of the juxtaglomerular (JG) cells in some steps leading to renin secretion, and raise the possibility that sulfhydryl reactivity might in part account for the stimulatory effects of organomercurial and other diuretics.