The fate of plasma kallikrein in normal and kininogen-deficient rats

The clearance of exogenous plasma kallikrein, its uptake by liver, spleen, kidneys, lungs and its extravasation in the paws were determined in normal Wistar rats, normal and kininogen-deficient Brown Norway rats. Kallikrein was purified from rat plasma and labelled with 125I. After intravenous injection of 125I-kallikrein, the disappearance of acid-precipitable kallikrein from the blood fits a biexponential curve similar in the three groups of rats: a rapid initial clearance (T1/2 around 3 min) followed by a phase of slower elimination (T1/2 around 50 min). Removal of kallikrein from the blood was associated with a large uptake of radioactivity by the liver: 67% of the 125I-kallikrein cleared from the blood at 10 min. The kidneys and the spleen accumulated small amounts of the radioactivity. The uptake of kallikrein by the spleen was slightly reduced in kininogen-deficient rats. The kininogen deficiency in Brown Norway rats from the strain BN/May Pfd was confirmed by the low levels of kinins released by tissue kallikrein and by a prolongation of activated thromboplastin times in the plasma of these animals. We concluded that plasma kallikrein is rapidly cleared from the circulation of the rat. The liver is the main clearing organ of plasma kallikrein. The disappearance of kallikrein from the circulation is not affected by the lack of high molecular weight kininogen, except in the case of the uptake of the enzyme performed by the cells of the spleen, which is reduced.