Zheng L, Chen J, Zhu Y, Yang H, Elmquist W, Hu M
Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Pullman 99164-6510.
Pharm Res. 1994 Dec;11(12):1771-6. doi: 10.1023/a:1018923618747.
Absorption mechanisms of L- and D-methionine (MET) in an in vitro cultured human intestinal epithelial cell model (Caco-2) and an in situ perfused rat intestinal model were investigated to determine if the kinetic characteristics of absorption are comparable in these two popular absorption models. The results indicate that the transport of L- and D-MET were concentration-dependent in both model systems, and displayed comparable Km values. The Km value for L-MET is 1.34 mM in the Caco-2 model and 3.6 mM in the perfused rat intestinal model, while the Km value for D-MET is 1.79 mM in the Caco-2 model and 2.87 mM in the perfused rat intestinal model. Although the Jmax values were not comparable because of significant methodology differences, the Jmax values for L-MET were always higher than that for D-MET. In addition, transport of L- and D-MET across the Caco-2 cell monolayers were also inhibited by 10 mM Phe and Lys while MeAIB, Pro and Glu were generally ineffective. Similar results were also observed with these inhibitors in the perfused rat intestinal model with the exception that a combination of Pro and Glu stimulated the uptake of L-MET. In conclusion, the transport characteristics of L- and D-MET are comparable in both model systems.
研究了L-和D-蛋氨酸（MET）在体外培养的人肠上皮细胞模型（Caco-2）和原位灌注大鼠肠道模型中的吸收机制，以确定这两种常用吸收模型中吸收的动力学特征是否具有可比性。结果表明，在两个模型系统中，L-和D-MET的转运均呈浓度依赖性，且Km值具有可比性。在Caco-2模型中，L-MET的Km值为1.34 mM，在灌注大鼠肠道模型中为3.6 mM；而在Caco-2模型中，D-MET的Km值为1.79 mM，在灌注大鼠肠道模型中为2.87 mM。尽管由于显著的方法学差异，Jmax值无可比性，但L-MET的Jmax值总是高于D-MET的Jmax值。此外，10 mM苯丙氨酸和赖氨酸也抑制L-和D-MET跨Caco-2细胞单层的转运，而甲基胺异丁酸、脯氨酸和谷氨酸通常无效。在灌注大鼠肠道模型中使用这些抑制剂也观察到类似结果，但脯氨酸和谷氨酸的组合刺激L-MET摄取这一情况除外。总之，在两个模型系统中，L-和D-MET的转运特征具有可比性。
