title: Clearance of the alpha 2 macroglobulin-trypsin complex and uptake of trypsin by perfused liver.
abstract: The uptake and degradation of the alpha 2 macroglobulin-trypsin (alpha 2 m-trypsin) complex have been studied using isolated liver cells but not in the liver as a whole. We report the clearance of the complex by the isolated and exsanguinated liver of Wistar male rats, weighing 150- 280 g, and compare it with that of the free enzyme. The hepatic clearance of the alpha 2m-trypsin complex follows a pattern with a distribution phase followed by an elimination phase, which contrasts with that of trypsin where only the distribution phase is observed. The extraction of trypsin from the perfusate is Ca(2+)-independent (156 +/- 14 pmol/g liver in the presence of 2.5 mM Ca2+, N = 9, versus 140 +/- 8 pmol/g liver in its absence, N = 7) and is not affected by 100 mM NH4Cl (152 +/- 7 pmol/g liver, N = 6), 100 U/ml heparin (164 +/- 14 pmol/g liver, N = 5), 30 microliters/ml carbon particle suspension (150 +/- 13 pmol/g liver, N = 7) or an acute-phase situation induced by turpentine (125 +/- 10 pmol/g liver, N = 6) (P > 0.05, ANOVA). The hepatic clearance of the alpha 2m-trypsin complex is Ca(2+)-dependent (1.8 +/- 0.2 ml/min in the presence of Ca2+, N = 8, versus 0.6 +/- 0.03 ml/min in its absence, N = 4), affected by NH4Cl (< 0.1 ml/min, N = 7), heparin (1.1 +/- 0.2 ml/min, N = 6) and the acute-phase (0.6 +/- 0.1 ml/min, N = 6) but not by the carbon particle suspension (1.8 +/- 0.2 ml/min, N = 7). These results show that trypsin is not internalized by hepatocytes (no NH4Cl effect) or Kupffer cells (no carbon particle effect) and that the alpha 2m-trypsin complex is internalized in a Ca(2+)-dependent process by hepatocytes, but not by Kupffer cells, and is affected by an acute-phase reaction.
authors.affiliation: Departamento de Bioquímica, Universidade Federal de São Paulo, Brasil.
authors.forename: M R
authors.initials: MR
authors.lastname: Nagaoka
authors.forename: M
authors.initials: M
authors.lastname: Kouyoumdjian
authors.forename: D R
authors.initials: DR
authors.lastname: Borges
mesh_terms: D000210:Acute-Phase Reaction; D000818:Animals; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D014357:Trypsin / Q000378:metabolism*; D000511:alpha-Macroglobulins / Q000378:metabolism*
chemical_list: C028939:alpha-2-macroglobulin-trypsin complex; D000511:alpha-Macroglobulins; D014357:Trypsin