Mizuma T, Masubuchi S, Awazu S
Department of Biopharmaceutics and Drug Rational Research Center, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji, Japan.
J Pharm Pharmacol. 1998 Feb;50(2):167-72. doi: 10.1111/j.2042-7158.1998.tb06172.x.
Intestinal absorption of four cyclic dipeptides was studied in the everted small intestine of the rat. Cyclic seryltyrosine (cyclo(Ser-Tyr)) was stable enough to be transported whereas linear seryltyrosine was not. The absorption clearance of cyclo(Ser-Tyr) was concentration-dependent, and for cyclo(Ser-Tyr) at 125 microM decreased in the presence of glycylsarcosine (10 mM) or cephalexin (10 mM), which were reported to be absorbed by oligopeptide transporter. The absorption clearance was also reduced at 4 degrees C and in the presence of 1 mM dinitrophenol. Kinetic analysis of cyclo(Ser-Tyr) absorption showed that Km and Vmax were 19.8 microM and 0.295 nmol min(-1) cm(-1), respectively. It was also suggested that cyclic aspartylphenylalanine and cyclic histidylphenylalanine were absorbed by oligopeptide transporters, but cyclic histidylproline was not. The absorption clearance of cyclo(Ser-Tyr) in the control was much higher than the value of the correlation line representing a plot of passive transport (which was obtained from the absorption clearance of cyclic peptides in the presence of glycylsarcosine (10 mM)) against hydrophobicity (oil-water partition coefficient). These results indicate that cyclo(Ser-Tyr) is absorbed by the oligopeptide transporter.
在大鼠外翻小肠中研究了四种环二肽的肠道吸收情况。环丝氨酰酪氨酸（环（Ser-Tyr））足够稳定，可以被转运，而线性丝氨酰酪氨酸则不能。环（Ser-Tyr）的吸收清除率呈浓度依赖性，在存在据报道可被寡肽转运体吸收的甘氨酰肌氨酸（10 mM）或头孢氨苄（10 mM）时，125 microM的环（Ser-Tyr）的吸收清除率降低。在4℃和存在1 mM二硝基苯酚的情况下，吸收清除率也降低。环（Ser-Tyr）吸收的动力学分析表明，Km和Vmax分别为19.8 microM和0.295 nmol min⁻¹ cm⁻¹。还表明环天冬氨酰苯丙氨酸和环组氨酰苯丙氨酸被寡肽转运体吸收，但环组氨酰脯氨酸不被吸收。对照中环（Ser-Tyr）的吸收清除率远高于代表被动转运的相关线的值（该值是从存在甘氨酰肌氨酸（10 mM）时环肽的吸收清除率与疏水性（油水分配系数）的关系图中获得的）。这些结果表明环（Ser-Tyr）被寡肽转运体吸收。
