H+-Dependent Transport Mechanism of Nateglinide in the Brush-Border Membrane of the Rat Intestine
H+-Dependent Transport Mechanism of Nateglinide in the Brush-Border Membrane of the Rat Intestine
复制标题
那格列奈在大鼠肠刷状缘膜中 H 依赖性转运机制
DOI：
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发表时间：
2005
影响因子：
3.5
通讯作者：
K. Iseki
中科院分区：
文献类型：
--
作者：
S. Itagaki;Y. Saito;Sayaka Kubo;Yukio Otsuka;Yutaro Yamamoto;Masaki Kobayashi;T. Hirano;K. Iseki
（-）- n -（反式-4-异丙基环己烷羰基）-d-苯丙氨酸（那格列奈）是一种新型的口服降糖药，其结构中含有一个羧基和一个肽型键。尽管口服那格列奈后迅速达到最大血清浓度，但那格列奈本身并不通过PepT1或MCT1运输。本研究的目的是表征小肠顶端的转运蛋白，这些转运蛋白负责那格列奈的快速吸收。大鼠肠刷状边界膜泡对那格列奈的摄取与质子耦合转运系统有关。头孢布烯竞争性地抑制H+依赖性那格列奈的摄取。甘氨酸肌氨酸（Gly-Sar）、头孢定和头孢氨苄没有显著抑制那格列奈的摄取。Gly-Sar和那格列奈联合使用大大降低了头孢布烯的摄取。联合治疗的效果明显大于单用Gly-Sar。此外，那格列奈竞争性地抑制H+驱动的头孢布烯转运体介导的头孢布烯摄取。头孢布烯的转运通过至少两个H+依赖的转运系统发生：一个是PepT1，另一个是头孢布烯/H+共转运系统。另一方面，我们证明了那格列奈转运通过一个H+依赖的单一系统发生，但与PepT1不同，可能与头孢丁酮/H+共转运系统相同。
(–)-N-(trans-4-Isopropylcyclohexanecarbonyl)-d-phenylalanine (nateglinide) is a novel oral hypoglycemic agent possessing a carboxyl group and a peptide-type bond in its structure. Although nateglinide quickly reaches the maximal serum concentration after oral administration, nateglinide itself is not transported by PepT1 or MCT1. The aim of this study was to characterize the transporters on the apical side of the small intestine that are responsible for the rapid absorption of nateglinide. The uptake of nateglinide by rat intestinal brush-border membrane vesicles is associated with a proton-coupled transport system. Ceftibuten competitively inhibited H+-dependent nateglinide uptake. Glycylsarcosine (Gly-Sar), cephradine, and cephalexin did not significantly inhibit the uptake of nateglinide. The combination of Gly-Sar and nateglinide greatly reduced the uptake of ceftibuten. The effect of the combined treatment was significantly greater than that of Gly-Sar alone. Furthermore, nateglinide competitively inhibited H+-driven ceftibuten transporter-mediated ceftibuten uptake. Ceftibuten transport occurs via at least two H+-dependent transport systems: one is PepT1, and the other is the ceftibuten/H+ cotransport system. On the other hand, we demonstrated that nateglinide transport occurs via a single system that is H+ dependent but is distinct from PepT1 and may be identical to the ceftibuten/H+ cotransport system.
过表达人肽转运蛋白 (hPEPT1) 的 CHO/hPEPT1 细胞作为拟肽药物的替代体外模型。
影响因子：
3.8
作者：
Han,HK;Rhie,JK;Oh,DM;Saito,G;Hsu,CP;Stewart,BH;Amidon,GL
通讯作者：
Amidon,GL
DOI：
10.1006/bbrc.1998.9298
发表时间：
1998-09-18
影响因子：
3.1
作者：
Balimane, PV;Tamai, I;Sinko, PJ
通讯作者：
Sinko, PJ
头孢氨苄上皮细胞通透性与肠道寡肽转运蛋白表达的相关性。
DOI：
--
发表时间：
2001
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Chu,XY;Sánchez-Castaño,GP;Higaki,K;Oh,DM;Hsu,CP;Amidon,GL
通讯作者：
Amidon,GL