Hepatocyte growth factor, blood clearance, organ uptake, and biliary excretion in normal and partially hepatectomized rats.

摘要: BACKGROUND Hepatocyte growth factor (HGF) (also known as scatter (SF)) is a heterodimeric protein that the most potent complete mitogen for hepatocytes in culture. HGF many epithelial cells including hepatocytes, kidney tubular cells, mammary keratinocytes, etc. The encoded by proto-oncogene c-met high affinity receptor HGF. concentration plasma dramatically increases after partial hepatectomy and fulminant hepatic failure. This study describes pharmacokinetics of rat. EXPERIMENTAL DESIGN Human recombinant (a gift from Genentech) was radioiodinated shown to retain biologic activity structure. Approximately 74 ng [125I]HGF injected into penile vein male Fisher rats 5 minutes bile fistula jugular venous catheterization were performed blood sampling. Half subjected 70% hepatectomy. RESULTS percentage radioactivity present liver control 29.5% +/- 0.5% at 15 decreased 8.6% 1.0% 120 minutes; kidneys had 6.2% 0.2% minutes, decreasing 1.48% 0.3% minutes. All other organs examined less than 1% radioactivity. remaining low sites blood, bone, muscle, skin. In rats, appeared within 3 reached peak between 40 50 tapered thereafter total 2-hour collection 2.3% 0.5%. partially hepatectomized clearance (partial = 0.27 0.03 ml/minute; 0.53 0.06 ml/minute, p < 0.006), terminal half-life prolonged 124 11 83 10 0.03). initial HGF, extrapolated chart, estimated 3.8 rats. CONCLUSIONS Liver principle organ uptake [125I]HGF; disappearance suggests multicompartment kinetics with rapid phase slower phase; only portion appears bile; decreases [125I]HGF. These results are correlated previous findings bearing on role elevation stimulus transfer G0 G1 early regeneration