Miyake Masateru, Fujishima Miki, Nakai Daisuke
Department of Pharmacy, Uppsala University.
BA Project, Formulation Research Institute, Otsuka Pharmaceutical Co., Ltd.
Biol Pharm Bull. 2017;40(9):1572-1575. doi: 10.1248/bpb.b17-00181.
We investigate the inhibitory effect of marketed drugs for treatment of inflammatory bowel disease (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD) on the uptake transporters of peptide transporter 1 (PEPT1), which are up-regulated under the inflamed condition. The uptake transport of glycylsarcosine, a typical substrate for PEPT1, was reduced to 60% only by 5-aminosalicylate at the clinically relevant concentration among tested marketed drugs in PEPT1 transfected HEK293 cell lines. These findings suggest that the inhibition of PEPT1, which were up-regulated in inflamed or non-inflamed site on UC and CD patients, contribute to the clinical effect of commercially available drugs for IBD patients through the inhibition of uptake of antigenic proinflammatory oligopeptides such as formyl-methionine (Met)-leucine (Leu)-phenylalanine (Phe) via PEPT1.
我们研究了用于治疗炎症性肠病（IBD）如溃疡性结肠炎（UC）和克罗恩病（CD）的市售药物对肽转运体1（PEPT1）摄取转运体的抑制作用，该转运体在炎症状态下上调。在PEPT1转染的HEK293细胞系中，在所测试的市售药物中，仅临床相关浓度的5-氨基水杨酸可将PEPT1的典型底物甘氨酰肌氨酸的摄取转运降低至6%。这些发现表明，UC和CD患者炎症或非炎症部位上调的PEPT1受到抑制，通过抑制抗原性促炎寡肽如甲酰甲硫氨酸（Met）-亮氨酸（Leu）-苯丙氨酸（Phe）经由PEPT1的摄取，有助于市售药物对IBD患者产生临床疗效。
