胆汁酸の肝細胞膜輸送に及ぼすグルカゴンの影響

Abstract

We have found that serum total bile acid (TBA) levels decreased in some patients with liver cirrhosis after intravenous administration of 1 mg glucagon. In the present study, the mechanism of this phenomenon was investigated in vitro using the hepatocyte culture system. The effect of the addition of glucagon on the membrane transport of ¹⁴C-taurocholic acid (¹⁴C-TCA) was studied in freshly isolated rat hepatocytes. The results were as follows : 1) Glucagon distinctly stimulated the release of cyclic AMP from hepatocytes in the standard medium. 2) Glucagon enhanced ¹⁴C-TCA uptake by hepatocytes in a concentration-dependent manner between 10⁻⁷～10⁻⁵ mol/L. 3) Dibutyryl cyclic AMP also enhanced the ¹⁴C-TCA uptake at the concentration of 10⁻⁵ or 2×10⁻⁵ mol/L. 4) The uptake curves of ¹⁴C-TCA by hepatocytes both with and without glucagon (10⁻⁶ mol/L) were linear until 120 seconds and reached a constant value by 900 seconds in the standard medium. However, in the Na⁺⁻free medium or in the ouabain-added standard medium, the uptakes were strongly depressed either with or without an addition of glucagon. 5) In a kinetic analysis, the hepatocytes uptake of ¹⁴C-TCA either with or without glucagon showed a saturation curve of the Michaelis-Menten type. With an addition of glucagon Vmax was increased, although the Km was unchanged. In conclusion, glucagon promoted the Na⁺⁻dependent active carrier-mediated transport in hepatocytes and increased their bile acids uptake.