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The Acetylcholinesterase Inhibitors Competitively Inhibited an Acetyl l-Carnitine Transport Through the Blood–Brain Barrier

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Abstract

We investigated the interaction of acetylcholinesterase (AChE) inhibitors with acetyl-l-carnitine (ALCAR) transporter at the blood–brain barrier (BBB). ALCAR uptake by conditionally immortalized rat brain capillary endothelial cell lines (TR-BBB cells), as an in vitro model of BBB, were characterized by cellular uptake study using [3H]ALCAR. In vivo brain uptake of [3H]ALCAR was determined by brain uptake index after carotid artery injection in rats. In results, the transport properties for [3H]ALCAR by TR-BBB cell were consistent with those of ALCAR transport by the organic cation/carnitine transporter 2 (OCTN2). Also, OCTN2 was confirmed to be expressed in the cells. The uptake of [3H]ALCAR by TR-BBB cells was inhibited by AChE inhibitors such as donepezil, tacrine, galantamine and rivastigmine, which IC50 values are 45.3, 74.0, 459 and 800 μM, respectively. Especially, donepezil and galantamine inhibited the uptake of [3H]ALCAR competitively, but tacrine and rivastigmine inhibited noncompetitively. Furthermore, [3H]ALCAR uptake by the rat brain was found to be significantly decreased by quinidine, donepezil and galantamine. Our results suggest that transport of AChE inhibitors such as donepezil and galantamine through the BBB is at least partly mediated by OCTN2 which is involved in transport of ALCAR.

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Acknowledgments

The authors wish to thank Dr. Terasaki for providing TR-BBB cell lines and Novartis International Pharmaceutical Ltd. for providing rivastigmine very kindly. This work was supported by the SRC Research Center for Women’s Diseases and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2011-0030701).

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  1. College of Pharmacy and Research Institute of Pharmaceutical Science, Sookmyung Women’s University, 52, Hyochangwon-gil, Yongsan-gu, Seoul, 140-742, Republic of Korea

    Na-Young Lee, Hyung-Ok Choi & Young-Sook Kang

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  1. Na-Young Lee
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Correspondence to Young-Sook Kang.

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Lee, NY., Choi, HO. & Kang, YS. The Acetylcholinesterase Inhibitors Competitively Inhibited an Acetyl l-Carnitine Transport Through the Blood–Brain Barrier. Neurochem Res 37, 1499–1507 (2012). https://doi.org/10.1007/s11064-012-0723-3

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