Department of Biopharmaceutics, Kyoto Pharmaceutical University, Japan.
Biol Pharm Bull. 2012;35(4):588-93. doi: 10.1248/bpb.35.588.
The variety of physiologic and biologic functions of zinc is fascinating and could be applicable to medicine. Our previous studies demonstrated that the absorption of zinc after oral administration to rats is dose-dependent. In order to clarify the detailed mechanism of the dose-dependent in vivo absorption, the transport of zinc across intestinal epithelial cells was investigated using Caco-2 monolayers and isolated rat intestinal membranes. The permeation of zinc across Caco-2 monolayers is concentration-dependent, and both saturable and nonsaturable components are involved. The Michaelis constant and maximum transport rate for saturable transport are 11.7 μM and 31.8 pmol min(-1) cm(-2), respectively; the permeability coefficient for nonsaturable trasnport is 2.37×10(-6) cm s(-1). These parameters for permeation across membranes isolated from duodenum, ileum, and jejunum of rats are similar with those of Caco-2 cells. The comparison of the parameters for permeation across isolated intestinal membrane suggests that the major site of intestinal zinc absorption in rats is the duodenum. The maximum rate of zinc transport across the isolated intestinal membrane (V(max)) shows no correlation with mRNA expression of ZIP4, ZIP5 or ZnT1 in rats, but shows an inverse correlation with that of metallothioneins (MTs). This finding may be partly explained by the buffering role of metallothionein in intestinal absorption. The saturable transport of zinc is not simply determined only by the influx transporter, ZIP4, since three influx and efflux transporters are involved in the transport of zinc.
锌的生理和生物学功能多种多样，令人着迷，可能适用于医学领域。我们之前的研究表明，大鼠经口服给予锌后，其吸收量与剂量呈正相关。为了阐明体内吸收呈剂量依赖性的详细机制，我们使用 Caco-2 单层细胞和分离的大鼠肠膜研究了锌在肠道上皮细胞中的跨膜转运。锌穿过 Caco-2 单层细胞的渗透是浓度依赖性的，涉及到可饱和和不可饱和的成分。可饱和转运的米氏常数和最大转运速率分别为 11.7 μM 和 31.8 pmol min(-1) cm(-2)；不可饱和转运的渗透率系数为 2.37×10(-6) cm s(-1)。这些参数对于从大鼠十二指肠、回肠和空肠分离的膜的渗透性与 Caco-2 细胞的参数相似。对分离肠膜渗透性参数的比较表明，大鼠肠道锌吸收的主要部位是十二指肠。分离肠膜上锌转运的最大速率（V(max)）与大鼠 ZIP4、ZIP5 或 ZnT1 的 mRNA 表达无相关性，但与金属硫蛋白（MTs）的表达呈负相关。这一发现部分可以解释为金属硫蛋白在肠道吸收中具有缓冲作用。锌的可饱和转运不仅仅由内流转运体 ZIP4 决定，因为三种内流和外流转运体都参与了锌的转运。
