Role of glandular kallikrein in the activation process of human plasma inactive renin.

Abstract

Completely inactive renin was isolated from normal human plasma by DEAE-Sepharose column chromatography and Blue-Sepharose column chromatography. This inactive renin had a molecular weight of 54,000 daltons as determined by gel filtration on Ultrogel AcA 44. When the inactive renin was activated by trypsin, its molecular weight decreased to 48,000 daltons. The trypsin-activated renin differed from a native form of active renin in plasma with respect to molecular weight (active renin, 43,000), pI value (active renin, 5.20; trypsin-activated renin, 5.06), km value (active renin, 60 nmoles/liter; trypsin-activated renin, 89 nmoles/liter), Ki value for pepstatin A (active renin, 2.6 mumoles/liter; trypsin-activated renin 5.0 mumoles/liter) and pH profile for angiotensin formation. Glandular kallikrein (human urinary or pig pancreatic) did not activate the inactive renin. When the trypsin-activated renin was treated with glandular kallikrein, its activity was unchanged, but its molecular and kinetic properties except pI value (trypsin-activated kallikrein-treated renin, 4.82) coincided with those of a native form of active renin in plasma. These results indicate that glandular kallikrein does not directly activate inactive renin but participates in the activation process of inactive renin. The results also suggest that inactive renin in human plasma is a renin precursor.