Saito Yoshitaka, Itagaki Shirou, Kubo Sayaka, Kobayashi Masaki, Hirano Takeshi, Iseki Ken
Department of Clinical Pharmaceutics and Therapeutics, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo, Nishi 6-chome, Kita-ku, Sapporo 060-0812, Japan.
Biochem Biophys Res Commun. 2006 Feb 17;340(3):879-86. doi: 10.1016/j.bbrc.2005.12.092. Epub 2005 Dec 27.
(-)-N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine (nateglinide) is a novel oral hypoglycemic agent possessing a peptide-type bond and a carboxyl group in its structure. Recently, we have shown that nateglinide transport occurs via the ceftibuten/H+ cotransport system, which is distinct from PepT1, and that the fluorescein/H+ cotransport system is involved in the uptake of nateglinide. The aim of this study was to characterize the functional properties of the intestinal nateglinide transporter. In the first part of this study, we demonstrated that the ceftibuten/H+ cotransport system is identical to the fluorescein/H+ cotransport system. We succeeded in purification of the nateglinide transporter from brush-border membranes of the rat small intestine using p-aminobenzoic acid (PABA)-affinity chromatography. We then investigated the functional properties of the nateglinide transporter using proteoliposomes prepared from the PABA-affinity chromatography elute. We demonstrated that nateglinide, ceftibuten, and fluorescein are transported by the same transporter in the intestine.
(-)-N-(反式-4-异丙基环己烷羰基)-D-苯丙氨酸（那格列奈）是一种新型口服降糖药，其结构中含有肽型键和羧基。最近，我们发现那格列奈的转运是通过头孢布烯/H⁺共转运系统进行的，该系统与肽转运体1（PepT1）不同，并且荧光素/H⁺共转运系统参与那格列奈的摄取。本研究的目的是表征肠道那格列奈转运体的功能特性。在本研究的第一部分，我们证明头孢布烯/H⁺共转运系统与荧光素/H⁺共转运系统相同。我们通过对氨基苯甲酸（PABA）亲和层析成功从大鼠小肠刷状缘膜中纯化出那格列奈转运体。然后，我们使用从PABA亲和层析洗脱物制备的蛋白脂质体研究那格列奈转运体的功能特性。我们证明那格列奈、头孢布烯和荧光素在肠道中由同一转运体转运。
