Hepatic uptake of hippurate: a multiple-indicator dilution, perfused rat liver study.

Hepatic uptake of hippurate: a multiple-indicator dilution, perfused rat liver study.
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马尿酸的肝脏摄取:多指标稀释、灌注大鼠肝脏研究。

DOI:
10.1152/ajpgi.1998.274.1.g10
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发表时间:
1998
期刊:
The American journal of physiology
影响因子:
--
通讯作者:
Pang,KS
Pang,KS
中科院分区:
--
文献类型:
--
作者:
Yoshimura,T;Schwab,AJ;Tao,L;Barker,F;Pang,KS

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用多指示剂稀释法(MID)研究了苯甲酸的甘氨酸偶联代谢产物马尿酸(HA)在大鼠肝脏单次灌流(12ml/−)中的肝转运。门静脉注射含有一组未消除的参比指示剂和[~3H]HA混合物的中剂量门静脉注射的[~3H]HA的静脉恢复显示存活分数为1,证实了原装HA没有从血浆中消失。当外流恢复符合Goresky等人的屏障限制模型时。题名/责任者/责任者/作者:A.投资。(52:991-1009,1973),发现导出的流入(Pins)和流出(Pout)渗透表面积乘积依赖于HA浓度(1-930μM),在低HA浓度下,PinSandPoutS是血浆流速的3.5倍,但随着HA浓度的增加而减小。然而,所有的值都大大超过了被动扩散的预期贡献,因为氯仿对HA缓冲液的平衡分配比非常低(在pH值7.4时为0.0001)。组织平衡分配系数(Pin/Pout,或流入/流出速率常数,K1/k−1)小于1,且随浓度的增加而减小。最优表观米氏常数和最大流速分别为182±60μM和12±4nmoL⋅S−1⋅g−1;流出时分别为390±190μM和29±13 nmoL⋅S−1⋅g−1。但在L-乳酸(20 MM)存在下,摄取HA的PINS(174±3μM)降低。苯甲酸(10-873μM)也能有效降低肝脏对HA的摄取(5.3±0.9μM)。这些相互作用表明,介导肝脏摄取乳酸和其他单羧酸的单羧酸转运体MCT2可能参与了HA的转运。
The hepatic transport of hippuric acid (HA), a glycine-conjugated metabolite of benzoic acid that exhibits only modest plasma albumin binding (binding association constant of 2.1 × 103M−1), was studied in the single-pass perfused rat liver (12 ml/min), using the multiple indicator dilution (MID) technique. The venous recovery of [3H]HA on portal venous injection of a MID dose containing a mixture of a set of noneliminated reference indicators and [3H]HA revealed a survival fraction of unity, corroborating the lack of disappearance of bulk HA from plasma. When the outflow recovery was fitted to the barrier-limited model of Goresky et al. (C. A. Goresky, G. G. Bach, and B. E. Nadeau.J. Clin. Invest. 52: 991–1009, 1973), the derived influx (PinS) and efflux (PoutS) permeability-surface area products were found to be dependent on the concentration of HA (1–930 μM);PinSandPoutSwere ∼3.5 times the plasma flow rate at low HA concentration, but decreased with increasing HA concentration. All values, however, greatly exceeded the expected contribution from passive diffusion, because the equilibrium distribution ratio of chloroform to buffer for HA was extremely low (0.0001 at pH 7.4). The tissue equilibrium partition coefficient (Pin/Pout, or ratio of influx to efflux rate constants,k1/k−1) was less than unity and decreased with concentration. The optimized apparent Michaelis-Menten constant and maximal velocity were 182 ± 60 μM and 12 ± 4 nmol ⋅ s−1⋅ g−1, respectively, for influx and 390 ± 190 μM and 29 ± 13 nmol ⋅ s−1⋅ g−1, respectively, for efflux. In the presence ofl-lactate (20 mM), however,PinSfor the uptake of HA (174 ± 3 μM) was reduced. Benzoic acid (10–873 μM) was also effective in reducing hepatic uptake of HA (5.3 ± 0.9 μM). These interactions suggest that MCT2, the monocarboxylate transporter that mediates the hepatic uptake of lactate and other monocarboxylic acids, may be involved in HA transport.
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