GLUTATHIONE AS A PRIMARY OSMOTIC DRIVING FORCE IN HEPATIC BILE FORMATION
GLUTATHIONE AS A PRIMARY OSMOTIC DRIVING FORCE IN HEPATIC BILE FORMATION
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DOI：
10.1152/ajpgi.1992.263.5.g617
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发表时间：
1992-11-01
影响因子：
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通讯作者：
TRUONG, AT
中科院分区：
文献类型：
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作者：
BALLATORI, N;TRUONG, AT
间接证据表明，谷胱甘肽（GSH）跨小管质膜转运进入胆汁有助于胆汁酸非依赖性部分胆汁流的形成。为了直接验证这一假设，本研究测量了离体灌流大鼠肝脏的胆汁流量，其胆汁GSH排泄率通过给予GSH单乙酯选择性地调节（50、100和200 mumol在20分钟间隔内输注），高剂量GSH本身（550 μ mol，20 min），以及GSH的三种氨基酸组分（各70 μ mol），含和不含蛋氨酸（35 μ mol）。使动物饥饿过夜以降低肝脏GSH水平，并用阿西霉素预处理肝脏以抑制γ-谷氨酰转移酶。用Krebs-Henseleit缓冲液单次灌注的肝脏以1-3 nmol的相对较低的速率排出胆汁酸。min-1。g-1，该速率不受用于改变胆汁GSH流出的试剂的影响。相比之下，基础胆汁GSH流出率为8-13 nmol·min-1。 G-1. GSH酯的给药产生了显著的剂量依赖性胆汁分泌，刺激胆汁GSH排泄，并导致完整GSH酯的胆汁排泄。总胆汁GSH排泄和胆汁流量的变化在时间和定量上相关。GSH和氨基酸补充剂的输注也导致更高的胆汁流量和胆汁GSH排泄率，但它们的作用更温和。胆汁流量的变化（mul-min-1 .g-1;纵坐标）与胆汁GSH排泄的伴随变化（nmol . min-1。g ~（-1）呈直线y = 0.034x + 0.067（r = 0.88），提示胆汁中1 μ mol GSH的排泄伴随着34穆尔胆汁的排泄。这些发现提供了直接的证据GSH作为渗透驱动力在肝胆汁的形成，并提供了一个估计的利胆效力，这三肽。
Indirect evidence suggests that transport of glutathione (GSH) across the canalicular plasma membrane into bile contributes to the formation of the bile acid-independent fraction of bile flow. To directly test this hypothesis, the present study measured bile flow in isolated perfused rat livers whose biliary GSH excretion rate was selectively modulated by administration of GSH monoethyl ester (50, 100, and 200 mumol infused over a 20-min interval), a high dose of GSH itself (550 mumol over 20 min), and the three amino acid components of GSH (70 mumol each) with and without methionine (35 mumol). Animals were starved overnight to decrease hepatic GSH levels, and livers were pretreated with acivicin to inhibit gamma-glutamyl transferase. Livers perfused single pass with Krebs-Henseleit buffer excreted bile acids at a relatively low rate of 1-3 nmol. min-1 . g-1, and this rate was unaffected by agents used to alter biliary GSH efflux. In comparison, basal biliary GSH efflux rates were 8-13 nmol-min-1. g-1. Administration of the GSH ester produced a dramatic dose-dependent choleresis, a stimulation of biliary GSH excretion, and resulted in the biliary excretion of intact GSH ester. Changes in total biliary GSH excretion and bile flow were temporally and quantitatively related. Infusion of GSH and amino acid supplementation also resulted in higher rates of bile flow and biliary GSH excretion, but their effects were more modest. A plot of the changes in bile flow (mul-min-1 .g-1; ordinate) vs. the accompanying changes in biliary GSH excretion (nmol . min-1 . g-1) demonstrated a relation described by the line y = 0.034x + 0.067 (r = 0.88), suggesting that biliary excretion of 1 mumol of GSH is accompanied by the excretion of 34 mul of bile. These findings provide direct evidence for GSH as an osmotic driving force in hepatic bile formation, and provide an estimate of the choleretic potency of this tripeptide.