Carrier-mediated transport of glycerol in the perfused rat small intestine
Carrier-mediated transport of glycerol in the perfused rat small intestine
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DOI：
10.1248/bpb.29.785
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发表时间：
2006-04-01
影响因子：
2
通讯作者：
Yuasa, H
中科院分区：
文献类型：
--
作者：
Ohta, KY;Inoue, K;Yuasa, H
最近，使用大鼠小肠的闭合环和外翻囊的研究提示，载体介导的转运参与甘油的肠吸收。虽然它可以介导的一种新的载体系统，很少的信息是可用的。本研究的目的是从动力学上表征载体介导的甘油在灌流大鼠小肠中的转运，以帮助识别所涉及的载体，并探索该载体可能用作口服药物递送途径和药物开发靶点的可能性。使用雄性Wistar大鼠的10 cm中肠段进行点燃原位单程灌注，并通过[H-3]甘油从肠腔中的消失来评价[H-3]甘油的吸收。甘油的吸收是饱和的，并通过从灌注溶液中去除Na+而显著降低，这表明涉及Na+依赖性载体介导的转运系统。通过假设Michaelis-Menten型载体介导转运和同时被动（扩散）转运，成功分析了浓度依赖性吸收曲线。最大转运速率（J（max））为77.0 pmol/s/cm（2），米氏常数（K-m）为1.04 m（M），J（max/）K（m）为7.39 × 10（-5）cm/s。被动转运的膜透性系数（P-m，P-d）为6.89 × 10 ~（-5）cm/s，略小于J（max）/K-m。因此，这可能是低浓度范围内肠甘油吸收的主要机制，其中载体介导的转运符合J（max）/K-m表示的线性动力学。此外，载体介导的甘油转运被发现抑制甘油3-磷酸，单乙酸甘油酯和双甘油，表明载体系统可能是由这些结构类似物共享。因此，本研究已经成功地证明和表征了载体介导的甘油在灌注大鼠小肠中的转运，这是一种生理相关的模型。
Studies using the closed loop and everted sacs of the rat small intestine recently prompted us to suggest that carrier-mediated transport is involved in the intestinal absorption of glycerol. Although it could be mediated by a novel carrier system, little information is available. The aim of the present stud), was to kinetically characterize carrier-mediated glycerol transport in the perfused rat small intestine to help in identifying the carrier involved and to explore the possibility that the carrier might be used as a pathway for oral drug delivery and a target for drug development. lit situ single-pass perfusion was conducted using a 10-cm midgut segment of the male Wistar rat, and the absorption of [H-3] glycerol was evaluated by its disappearance from the intestinal lumen. The absorption of glycerol was saturable and significantly reduced by removing Na+ from the perfusion solution, suggesting the involvement of a Na+-dependent carrier-mediated transport system. The concentration-dependent absorption profile was successfully analyzed by assuming Michaelis-Menten type carrier-mediated transport and simultaneous passive (diffusive) transport. The maximum transport rate (J(max)) was 77.0 pmol/s/cm(2) and the Michaelis constant (K-m) was 1.04 m(M), giving a J(max/)K(m) of 7.39 X 10(-5) cm/s. The membrane permeability coefficient for passive transport (P-m,P-d) was 6.89X10(-5)cm/s, slightly smaller than J(max)/K-m. Therefore, it could be the major mechanism of intestinal glycerol absorption in the low concentration range where carrier-mediated transport conforms to linear kinetics represented by J(max)/K-m. Furthermore, carrier-mediated glycerol transport was found to be inhibited by glycerol 3-phosphate, monoacetin and diglycerol, indicating that the carrier system may be shared by these structural analogues. Thus, the present study has successfully demonstrated and characterized carrier-mediated glycerol transport in the perfused rat small intestine which is a physiologically relevant model.