Divergent developmental expression and function of the proton-coupled oligopeptide transporters PepT2 and PhT1 in regional brain slices of mouse and rat.
Divergent developmental expression and function of the proton-coupled oligopeptide transporters PepT2 and PhT1 in regional brain slices of mouse and rat.
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DOI：
10.1111/jnc.12687
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发表时间：
2014-06
影响因子：
4.7
通讯作者：
Smith DE
中科院分区：
文献类型：
--
作者：
Hu Y;Xie Y;Keep RF;Smith DE
本研究评价了质子偶联寡肽转运体（POTs：PepT 1，PepT 2，PhT 1和PhT 2）在啮齿动物脑不同区域的发育基因和蛋白表达，以及POT底物甘氨酰肌氨酸在脑切片中的年龄依赖性摄取。从野生型和PepT 2缺失小鼠的大脑皮层、小脑和下丘脑以及从不同年龄的大鼠获得切片。通过实时PCR和免疫印迹分析确定基因和蛋白质表达。脑切片摄取的放射性标记的glycylsarcosine测定存在和不存在过量的未标记的glycylsarcosine或L-组氨酸，后者是一种抑制剂的PhT 1/2，但不是PepT 1/2。尽管PepT 2和PhT 1转录本在小鼠脑的所有三个区域中大量表达，但几乎没有观察到PepT 1和PhT 2的表达。PhT 1蛋白存在于成年小鼠的大脑区域，但不存在于新生小鼠的大脑区域，并且在大鼠中表达水平随着年龄的增长而增加。甘氨酰肌氨酸的摄取，抑制和转运蛋白的优势没有表现出区域脑或物种的差异。然而，在功能活动方面存在明显的年龄相关差异，PepT 2在新生小鼠和大鼠中占主导地位，PhT 1在成年啮齿动物中占主导地位。这些发育变化可能会显着影响内源性和外源性（药物）肽/模拟物的神经活性。
This study evaluated the developmental gene and protein expression of proton-coupled oligopeptide transporters (POTs: PepT1, PepT2, PhT1 and PhT2) in different regions of rodent brain, and the age-dependent uptake of a POT substrate, glycylsarcosine, in brain slices. Slices were obtained from cerebral cortex, cerebellum and hypothalamus of wildtype and PepT2 null mice, and from rats at different ages. Gene and protein expression were determined by real-time PCR and immunoblot analyses. Brain slice uptakes of radiolabeled glycylsarcosine were determined in the absence and presence of excess unlabeled glycylsarcosine or L-histidine, the latter being an inhibitor of PhT1/2 but not PepT1/2. Whereas PepT2 and PhT1 transcripts were abundantly expressed in all three regions of mouse brain, little to no expression was observed for PepT1 and PhT2. PhT1 protein was present in brain regions of adult but not neonatal mice and expression levels increased with age in rats. Glycylsarcosine uptake, inhibition and transporter dominance did not show regional brain or species differences. However, there were clear age-related differences in functional activity, with PepT2 dominating in neonatal mice and rats, and PhT1 dominating in adult rodents. These developmental changes may markedly impact the neural activity of both endogenous and exogenous (drug) peptides/mimetics.
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影响因子：
4.7
作者：
Hu, Yongjun;Shen, Hong;Smith, David E.
通讯作者：
Smith, David E.
影响因子：
4.7
作者：
Novotny, A;Xiang, J;Keep, RF
通讯作者：
Keep, RF
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作者：
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通讯作者：
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影响因子：
4.8
作者：
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通讯作者：
Brosius, FC
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3.9
作者：
Jappar, Dilara;Wu, Shu-Pei;Smith, David E.
通讯作者：
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