PLASMA KALLIKREIN AND THROMBIN ARE CLEARED THROUGH UNRELATED HEPATIC PATHWAYS

Plasma kallikrein (PK) and thrombin (TH), serine proteinases formed fr om inactive precursors, participate in important body defence mechanis ms. The isolated hepatocyte recognizes TH, and the liver clears PK by calcium-independent receptors through mechanisms that are not yet clea rly understood. It is known that heparin impairs the binding of TH to isolated liver cells through the inhibition of high affinity receptors . Using an isolated, exsanguinated and perfused rat liver preparation we confirmed that the TH hepatic clearance is calcium-independent and affected by heparin; PK clearance rates both in the presence (t1/2 10 +/- 2 min) or the absence (t1/2 10 +/- 1 min) of heparin were similar; the presence of beta-galactosides does not impair the TH clearance bu t adversely affects the PK clearance and a large excess of TH does not impair the PK clearance rate (t1/2 6 +/- 1 min). These results indica te that PK and TH are cleared by calcium-independent but otherwise unr elated hepatic pathways and suggest that TH may indeed facilitate the PK clearance by the liver.