Rat plasma kallikrein clearance by perfused rat liver.

Previous studies have shown that perfused rat liver in situ is able to clear recirculating rat plasma kallikrein (RPK) in two phases: an initial clearance lasting a few minutes, followed by a slow exponential phase. Using purified RPK preparations we now show that: RPK is a glycoprotein; clearance was inhibited by human serum against blood group B and 0.1 M melibiose but was not affected by human serum against blood group A, 0.1 M lactose, 0.1 M mannose, 0.05 M N-acetyl galactosamine, 0.05 M galactose or 15 microM asialofetuin. Prolonged incubation of RPK with alpha-galactosidase reduced RPK clearance. Oligosaccharide structures in RPK may have terminal galactose units since treatment of RPK with neuraminidase did not affect the clearance rate; RPK clearance occurs in the absence of added Ca2+, with either EDTA or EGTA in the perfusion fluid; the exponential phase is reversibly inhibited by the addition of NH4Cl or chloroquine to the perfusion fluid. This observation, along with experiments using liver homogenates, suggests that RPK catabolism is carried out by lysosomal enzymes, probably cathepsin B of possible hepatocyte origin.