Human renin activation by protease from the renin granule fraction of the dog kidney cortex.
To clarify the possible conversion of prorenin in renin granules where conversion reportedly occurred, we investigated whether the renin granule fraction of the kidney could activate prorenin to the active form. Renin granules were isolated from the dog kidney cortex by discontinuous sucrose density gradient centrifugation. Human active renin was quantified by immunoradiometric assay which could detect only the human active renin but not the inactive human renin or dog renin. Inactive renin from human amniotic fluid was incubated with the subcellular fraction of the dog kidney cortex. The renin granule fraction that showed the highest renin activity stimulated the inactive renin to become the active form. The membrane preparation obtained from the renin granule fraction by freezing and thawing the fraction in low osmolarity retained the activity of renin activation. Other subcellular fractions showed less renin activation. The optimal pH for renin activation by the membrane was pH 5.0 to 6.0. The activation depended on the time of incubation and concentration. The activation was inhibited by N-ethylmaleimide but not by EDTA or serine protease inhibitors. These results suggest that renin is processed by a membrane bound protease in renin granules.
Ikeda
M
M
Department of Internal Medicine and Biochemistry, Fukuoka University School of Medicine, Japan.
Oda
K
K
Tsuji
E
E
Noda
K
K
Sasaguri
M
M
Ideishi
M
M
Arakawa
K
K
D000653:Amniotic Fluid / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002846:Chromatography, Affinity; D003594:Cytoplasmic Granules / Q000201:enzymology* / Q000378:metabolism; D004285:Dogs; D010450:Endopeptidases / Q000378:metabolism*; D004792:Enzyme Precursors / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007672:Kidney Cortex / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D012083:Renin / Q000378:metabolism*
D004792:Enzyme Precursors; D011480:Protease Inhibitors; D010450:Endopeptidases; D012083:Renin