Journal of Clinical Endocrinology & Metabolism, Vol 51, 942-944, Copyright © 1980 by Endocrine Society

ARTICLES

Renin requires a structural alteration prior to activation by renal kallikrein

WA Hsueh, EJ Carlson, D O'Connor and S Warren

Renal kallikrein may be the physiologic protease which activates renin. In vitro activation of plasma inactive renin by renal kallikrein, however, requires prior dialysis of plasma to pH 3.3, which is thought to destroy endogenous plasma kallikrein inhibitors. We present evidence that low pH directly alters renin to facilitate its activation by renal kallikrein. Untreated normal plasma was combined with pH 3.3 dialyzed and neutralized plasma and incubated with semipurified human renal kallikrein 2.3 X 10(-2) to 4.6 IU/ml, pH 7.5, 25 degrees C for 1h. All concentrations activated renin in acid-treated plasma; whereas, in untreated plasma 4.6 IU/ml renal kallikrein was ineffective. In combinations of untreated and acid-treated plasma, the percent renin activated by renal kallikrein was equal to the percent acid-dialyzed plasma present. When acid-treated plasma was combined with buffer, activation was complete and quantitatively the same as in the untreated and acid-treated plasma combinations. The data suggest inactive renin itself is altered structurally by pH 3.3; this change in the renin molecule is necessary for kallikrein activation. Renal kallikrein may not be the sole in vivo activator of renin.