title: Plasma kallikrein and thrombin are cleared through unrelated hepatic pathways.
abstract: Plasma kallikrein (PK) and thrombin (TH), serine proteinases formed from inactive precursors, participate in important body defence mechanisms. The isolated hepatocyte recognizes TH, and the liver clears PK by calcium-independent receptors through mechanisms that are not yet clearly 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 but 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 indicate that PK and TH are cleared by calcium-independent but otherwise unrelated hepatic pathways and suggest that TH may indeed facilitate the PK clearance by the liver.
authors.affiliation: Department of Medicine (Division of Gastroenterology), Escola Paulista de Medicina, Sao Paulo, Brazil.
authors.forename: M R
authors.initials: MR
authors.lastname: Loureiro-Silva
authors.forename: M
authors.initials: M
authors.lastname: Kouyoumdjian
authors.forename: D R
authors.initials: DR
authors.lastname: Borges
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D037263:Asialoglycoprotein Receptor; D005697:Galactosides / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D007610:Kallikreins / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008969:Molecular Sequence Data; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013917:Thrombin / Q000378:metabolism*
chemical_list: D037263:Asialoglycoprotein Receptor; D005697:Galactosides; D011956:Receptors, Cell Surface; D006493:Heparin; D007610:Kallikreins; D013917:Thrombin