Rat renal and plasma prorenin are activated in vitro by different mechanisms

The aim of the present study was to purify and identify a plasma protein fr action (PreR-Co) involved in renal prorenin activation and to explore its c apacity to process plasma prorenin. PreR-Co was obtained from plasma as a s ingle electrophoretic band by (NH4)(2)SO4 precipitation, Sephacryl S-200 HR gel filtration, anti-rat: albumin immunoaffinity, and ion-exchange chromat ography. The amidase, esterase, and kallikrein activities of PreR-Co were s tudied, as was its N-terminal amino acid sequence. Rat kidney extract or pl asma (normal or previously treated with acid to pH 2.8) were incubated with PreR-Co for 15 minutes at 37 degrees C. Renin concentration was measured b y incubation with homologous angiotensinogen. The same protocol was repeate d with samples activated by trypsin. The N-terminal amino acid sequence was IIGGSMDAKGSFP, which had a homology of 90% with the beta-chain of haptoglo bin, 69% with serine-proteases, and 65% with kallikreins. The renin concent ration in rat kidney extract was 34+/-4 ng of angiotensin I (Ang I) mg of t issue(-1).h(-1). After PreR-Co or trypsin treatments, renin concentrations were 211+/-7 and 110+/-11 ng of Ang I mg of tissue(-1).h(-1), respectively. The plasma renin concentration in normal plasma was 67.6+/-13.3 ng of Ang I.mL(-1).h(-1), and no significant difference was observed after PreR-Co tr eatment. However, a significant increase (202.8+/-7.8 ng of Ang I.mL(-1).h( -1); P<0.01) was found after trypsin treatment. The isolated PreR-Co acts o n renal prorenin but not on plasma prorenin. These results suggest that act ive renin is processed in the kidney by a circulating enzyme that may have a role in the regulation of circulating renin.