PLASMA KALLIKREIN AND TISSUE-TYPE PLASMINOGEN-ACTIVATOR COMPETE FOR ACOMMON PATHWAY INTO THE LIVER

The liver is the main organ used to clear both tissue and plasma kalli kreins from the circulation. Rat plasma kallikrein (rPK) is internaliz ed by hepatocytes by a receptor-mediated mechanism. Since plasma kalli krein and tissue-type plasminogen activator (tPA) are both important f or fibrinolysis, we now compare characteristics of the clearance of bo th by the isolated, exsanguinated and perfused rat liver. In prelimina ry experiments we observed, in vitro, that rPK and tPA neither form a complex with, nor are they substrates for, each other. The characteris tics of rPK and tPA clearance are similar, and we observed that 20 and 200 molar excess of tPA in the perfusion medium decreased and abolish ed the rPK liver clearance, respectively. These results suggest that r PK and tPA share a common pathway for liver clearance.