Ricci G L, Michiels R, De Groote J, Fevery J
Department of Medical Research, Catholic University of Leuven, Belgium.
Arch Int Pharmacodyn Ther. 1992 Nov-Dec;320:93-102.
Intravenous infusion of glucagon (100 micrograms/hr/100 g body weight) in rats produces a 20 to 35% increase in bile flow and enhances the activity of hepatic bilirubin uridine diphosphate-glucuronyltransferase to 132% after a 90 min infusion. When a bilirubin load is given to produce a constant and apparently maximal biliary bilirubin excretion rate (or transport maximum) the administration of glucagon increased the bilirubin transport maximum. The excretion rate of bilirubin monoglucuronides was more enhanced than that of diglucuronide. The enhanced rate of glucuronidation, assayed in vitro, correlated with the augmented biliary output and inversely with the plasma unconjugated bilirubin levels. It is concluded that glucagon, at the dosage used, leads to a higher formation rate of bilirubin monoconjugates and that the choleresis, also induced by the hormone, enhances the biliary secretion of the monoconjugates formed. The enhanced conjugation results in a decreased plasma concentration of unconjugated bile pigment and the associated choleresis leads to a decreased di- to monoconjugate ratio, opposite to what has been observed during bilirubinostasis and cholestasis. The secretory efficacy, as assessed from the bile-to-plasma concentration ratio, is enhanced for all bilirubin pigments after glucagon administration.
给大鼠静脉输注胰高血糖素(100微克/小时/100克体重),可使胆汁流量增加20%至35%,并在输注90分钟后将肝脏胆红素尿苷二磷酸 - 葡萄糖醛酸转移酶的活性提高至132%。当给予胆红素负荷以产生恒定且明显最大的胆汁胆红素排泄率(或转运最大值)时,给予胰高血糖素可增加胆红素转运最大值。单葡萄糖醛酸胆红素的排泄率比双葡萄糖醛酸胆红素的排泄率提高得更多。体外测定的葡萄糖醛酸化增强率与胆汁输出增加相关,与血浆未结合胆红素水平呈负相关。得出的结论是,所用剂量的胰高血糖素导致胆红素单结合物的形成率更高,并且该激素诱导的胆汁分泌增多增强了所形成的单结合物的胆汁分泌。结合增强导致未结合胆色素的血浆浓度降低,而相关的胆汁分泌增多导致双结合物与单结合物的比例降低,这与胆红素稳态和胆汁淤积期间观察到的情况相反。从胆汁与血浆浓度比评估,胰高血糖素给药后所有胆红素色素的分泌效率均提高。