Peptide transporter 1 is responsible for intestinal uptake of the dipeptide glycylsarcosine: studies in everted jejunal rings from wild-type and Pept1 null mice.
Peptide transporter 1 is responsible for intestinal uptake of the dipeptide glycylsarcosine: studies in everted jejunal rings from wild-type and Pept1 null mice.
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DOI：
10.1002/jps.22277
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发表时间：
2011-02
影响因子：
3.8
通讯作者：
Smith, David E.
中科院分区：
文献类型：
--
作者：
Ma, Katherine;Hu, Yongjun;Smith, David E.
关键词：
本研究的目的是确定PEPT 1在使用甘氨酰肌氨酸（GlySar）从小鼠小肠摄取肽/模拟物中的相对重要性。从野生型和Pept 1缺失小鼠中分离空肠组织后，将2厘米的肠段翻转并安装在玻璃棒上进行组织吸收研究。研究了[14C] GlySar（4 μ M）与时间、温度、钠和pH值、浓度和潜在抑制剂的关系。与野生型动物相比，Pept1敲除小鼠在pH 6.0、37 ° C下显示出78%的GlySar摄取减少。GlySar摄取显示pH依赖性，野生型动物的峰值在pH 6.0 - 6.5之间，而在Pept1敲除小鼠中未观察到这种趋势。GlySar在野生型动物中表现出Michaelis-Menten摄取动力学和次要的不饱和组分。相反，GlySar摄取发生在Pept1基因敲除小鼠中仅通过非饱和过程。GlySar摄取被二肽、氨基头孢菌素、血管紧张素转换酶抑制剂和抗病毒前药伐昔洛韦显著抑制;这些抑制剂对Pept1缺失小鼠GlySar摄取的影响很小（如果有的话）。结果表明，PEPT1在空肠摄取GlySar中起着关键作用，并表明PEPT1是负责小肠吸收小肽的主要转运蛋白。
The purpose of this study was to determine the relative importance of PEPT1 in the uptake of peptides/mimetics from mouse small intestine using glycylsarcosine (GlySar). After isolating jejunal tissue from wild-type and Pept1 null mice, 2-cm intestinal segments were everted and mounted on glass rods for tissue uptake studies. [14C]GlySar (4 μM) was studied as a function of time, temperature, sodium and pH, concentration, and potential inhibitors. Compared to wild-type animals, Pept1 null mice exhibited a 78% reduction of GlySar uptake at pH 6.0, 37°C. GlySar uptake showed pH dependence with peak values between pH 6.0-6.5 in wild-type animals, while no such tendency was observed in Pept1 null mice. GlySar exhibited Michaelis-Menten uptake kinetics and a minor nonsaturable component in wild-type animals. In contrast, GlySar uptake occurred by only a nonsaturable process in Pept1 null mice. GlySar uptake was significantly inhibited by dipeptides, aminocephalosporins, angiotensin-converting enzyme inhibitors, and the antiviral prodrug valacyclovir; these inhibitors had little, if any, effect on the uptake of GlySar in Pept1 null mice. The findings demonstrate that PEPT1 plays a critical role in the uptake of GlySar in jejunum, and suggest that PEPT1 is the major transporter responsible for the intestinal absorption of small peptides.
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影响因子：
4.8
作者：
RONG, LA;FEI, YJ;LEIBACH, FH
通讯作者：
LEIBACH, FH
影响因子：
3.7
作者：
Hironaka, Takanori;Itokawa, Shota;Kimura, Toshikiro
通讯作者：
Kimura, Toshikiro
影响因子：
3.9
作者：
Kato, Yukio;Sugiura, Tomoko;Tsuji, Akira
通讯作者：
Tsuji, Akira
影响因子：
4.9
作者：
Hu Y;Smith DE;Ma K;Jappar D;Thomas W;Hillgren KM
通讯作者：
Hillgren KM
DOI：
10.1124/jpet.103.057109
发表时间：
2004-03-01
影响因子：
3.5
作者：
Hatanaka, T;Haramura, M;Ganapathy, ME
通讯作者：
Ganapathy, ME