Plasma kallikrein and tissue-type plasminogen activator compete for a common pathway into the liver

• Published in: Immunopharmacology Vol. 32; no. 1-3; pp. 88 - 90
• Main Authors: Nagaoka, Marcia R, Kouyoumdjian, Maria, Borges, Durval R
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.1996
• Subjects: Animals; Binding, Competitive - physiology; In Vitro Techniques; Kallikreins - metabolism; Liver; Liver - enzymology; Liver - metabolism; Liver receptor; Plasma kallikrein; Rats; Tissue Plasminogen Activator - metabolism; Tissue-type plasminogen activator; BSA, bovine serum albumin; Liver receptor; rPK, rat plasma kallikrein; Tissue-type plasminogen activator; Liver; EC, sinusoidal endothelial liver cells; Plasma kallikrein; pNA, p-nitroanilide; DMSO, dimethyl sulfoxide; tPA, tissue-type plasminogen activator; KC, Kupffer cells; PC, parenchymal liver cells
• ISSN: 0162-3109
• DOI: 10.1016/0162-3109(96)88182-3

The liver is the main organ used to clear both tissue and plasma kallikreins from the circulation. Rat plasma kallikrein (rPK) is internalized by hepatocytes by a receptor-mediated mechanism. Since plasma kallikrein and tissue-type plasminogen activator (tPA) are both important for fibrinolysis, we now compare characteristics of the clearance of both by the isolated, exsanguinated and perfused rat liver. In preliminary experiments we observed, in vitro, that rPK and tPA neither form a complex with, nor are they substrates for, each other. The characteristics of rPK and tPA clearance are similar, and we observed that 20 and 200 molar excess of tPA in the perfusion medium decreased and abolished the rPK liver clearance, respectively. These results suggest that rPK and tPA share a common pathway for liver clearance.