Teuscher Nathan S, Shen Hong, Shu Cathaleen, Xiang Jianming, Keep Richard F, Smith David E
Department of Pharmaceutical Sciences, College of Pharmacy, and Upjohn Center for Clinical Pharmacology, The University of Michigan, Ann Arbor, Michigan 48109, USA.
J Neurochem. 2004 Apr;89(2):375-82. doi: 10.1111/j.1471-4159.2004.02333.x.
PEPT2 is functionally active and localized to the apical membrane of rat choroid plexus epithelial cells. However, little is known about the transport mechanisms of endogenous neuropeptides in choroid plexus, and the role of PEPT2 in this process. In the present study, we examined the uptake kinetics of carnosine in rat choroid plexus primary cell cultures and choroid plexus whole tissue from wild-type (PEPT2(+/+)) and null (PEPT2(-/-)) mice. Our results indicate that carnosine is preferentially taken up from the apical as opposed to basolateral membrane of cell monolayers, and that basolateral efflux in limited. Transepithelial flux of carnosine was not distinguishable from that of paracellular diffusion. The apical uptake of carnosine was characterized by a high affinity (K(m) = 34 microM), low capacity (V(max) = 73 pmol/mg protein/min) process, consistent with that of PEPT2. The non-saturable component was small (K(d) = 0.063 microL/mg protein/min) and, under linear conditions, was only 3% of the total uptake. Studies in transgenic mice clearly demonstrated that PEPT2 was responsible for over 90% of carnosine's uptake in choroid plexus whole tissue. These findings elucidate the unique role of PEPT2 in regulating neuropeptide homeostasis at the blood-cerebrospinal fluid interface.
肽转运体2（PEPT2）功能活跃，定位于大鼠脉络丛上皮细胞的顶端膜。然而，关于脉络丛中内源性神经肽的转运机制以及PEPT2在此过程中的作用，人们了解甚少。在本研究中，我们检测了肌肽在野生型（PEPT2(+/+)）和基因敲除型（PEPT2(-/-)）小鼠的大鼠脉络丛原代细胞培养物和脉络丛全组织中的摄取动力学。我们的结果表明，与细胞单层的基底外侧膜相比，肌肽优先从顶端膜摄取，且基底外侧流出有限。肌肽的跨上皮通量与细胞旁扩散的通量没有区别。肌肽的顶端摄取具有高亲和力（K(m)=34 microM）、低容量（V(max)=73 pmol/mg蛋白/分钟）的特点，这与PEPT2一致。非饱和成分较小（K(d)=0.063微升/mg蛋白/分钟），在线性条件下，仅占总摄取量的3%。对转基因小鼠的研究清楚地表明，PEPT2负责脉络丛全组织中超过90%的肌肽摄取。这些发现阐明了PEPT2在调节血脑脊液界面神经肽稳态中的独特作用。
