Subcellular distribution of low- and high-molecular-weight renin and its relation to a renin inhibitor in pig renal cortex.

1. The subcellular distribution of low-molecular-weight and high-molecular weight forms of pig renin has been investigated. 2. Renin, in aqueous extracts of a 'renin granular fraction' prepared by differential centrifugation, after gel filtration on Sephadex G-100 displayed an apparent molecular weight of 40 000 and was not activated by acidification to pH 2.8. 3. Renin in the soluble fraction separated on Sephadex G-100 at neutral pH displayed a main peak of activity with an apparent molecular weight of 40 000. When eluates were acidified to pH 2.8 (2 degrees C, 60 min) a marked increase in renin activity was observed in the region corresponding to an apparent molecular weight of 50 000. 4. A renin inhibitory material was isolated from the soluble fraction by DEAE chromatography. This material displayed an apparent molecular weight of 50 000 and it was destroyed by acidification to pH 2.8. 5. The presence of the proteolytic inhibitor N-ethylmaleimide yielded an apparently high-molecular-weight form of renin (60 000--70 000) from the soluble fraction, but this was not found in the granular fraction. 6. We conclude that pig renal renin is stored within membrane-bounded subcellular organelles as the low-molecular-weight form. High-molecular-weight renin and renin inhibitory activity are localized to the cortical soluble fraction. In addition, the soluble fraction contains a material which in the presence of N-ethylmaleimide results in the formation of an apparently high-molecular-weight renin.