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标题：The Influence of Glucagon on the Hepatic Transport of Taurocholate in Isolated Perfused Rat Liver : Kinetic Analysis by the Multiple Indicator Dilution Technique
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作者：Seiji MIYAUCHI ; Yasufumi SAWADA ; Tatsuji IGA 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1993
卷号：16
期号：8
页码：791-795
DOI：10.1248/bpb.16.791
出版社：The Pharmaceutical Society of Japan
摘要：Glucagon has been demonstrated to stimulate the uptake of bile acid in isolated rat hepatocytes (Am. J. Physiol., 249, G427(1985)). In the present study, we determined the influence of glucagon on the hepatic transport of a bile acid, taurocholate (TCA), in isolated rat livers. A single-pass perfusion and a rapid-injection, multiple indicator dilution method were employed. The hepatic availability at steady-state was 0.04. With the presence of glucagon in the perfusate(from 10^-9 to 10^-7M), the bile flow rate was stimulated by 30%, while hepatic availability was decreased from 0.04 to 0.02 with a stepwise increase in glucagon concentration. Thirty min after the infusion glucagon (300nM), [³H]TCA and [¹⁴C]inulin were injected in a bolus state into the portal vein, and the outflow was collected at 1.0s intervals over 30s. Glucagon decreased the instantaneous hepatic availability by 50% compared to the control level, and was thus compatible with the steady-state experiments. In the control experiment, the influx clearance (PS_inf) was 20 times higher than the efflux clearance (PS_eff). Glucagon (300nM) in the perfusate enhanced PS_inf by 50% of the control, whereas sequestration clearance (CL_seq) and the biliary excretion rate constant remained unchanged. PS_eff was stimulated to 2 times the control, but still remained much smaller than CL_seq. Based on the comparison of PS_inf, PS_eff and CL_seq, the rate-determining process of TCA hepatic elimination was the influx process in both the presence and absence of glucagon. Taken together, the enhancement of the influx process was responsible for the decrease in TCA hepatic availability caused by glucagon. Glucagon also enhanced the bile flow rate, but did not alter the biliary excretion rate of TCA, suggesting that glucagon might stimulate the bile acid independent bile flow.
关键词：taurocholate;glucagon;multiple indicator dilution technique;liver perfusion