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MKC-231, a choline uptake enhancer: (3) mode of action of MKC-231 in the enhancement of high-affinity choline uptake

  • Alzheimer's Disease and Related Disorders - Original Article
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Abstract

MKC-231, a putative cholinergic activity, is reported to improve learning and memory impaired in AF64A-treated animals. MKC-231 enhances high-affinity choline uptake (HACU) known as the rate-limiting step of acetylcholine (ACh) synthesis. We investigated the mode of action (MOA) of HACU enhancement by MKC-231. Intracerebroventricular (i.c.v.) injections of AF64A (3 nmol/brain) resulted in significant HACU reduction in hippocampal synaptosomes. Treatment with MKC-231 increased V max of HACU and B max of [3H]-HC-3 binding 1.6 and 1.7-fold, respectively. In studies of [3H]-MKC-231 binding and Biacore analysis, MKC-231 showed noticeable affinity for cloned high-affinity choline transporters (CHT1). The present study suggests that MKC-231 directly affects trafficking of CHT1 and increases the numbers of transporter, working for HACU, at the synaptic membrane.

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Authors and Affiliations

  1. Pharmacology Department IV, Pharmacology Laboratory, Research Division, Mitsubishi Tanabe Pharma Corporation, 1000, Kamoshida-cho, Aoba-ku, Yokohama, 227-0033, Japan

    Ken Takashina, Tomoko Bessho, Reiko Mori & Junichi Eguchi

  2. Lead Generation Research Department, Medicinal Chemistry Laboratory, Research Division, Mitsubishi Tanabe Pharma Corporation, Yokohama, Japan

    Kunji Kawai

  3. Global Product Strategy Department, Mitsubishi Tanabe Corporation, Tokyo, Japan

    Ken-Ichi Saito

Authors
  1. Ken Takashina
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  2. Tomoko Bessho
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  3. Reiko Mori
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  4. Kunji Kawai
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  5. Junichi Eguchi
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  6. Ken-Ichi Saito
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Correspondence to Ken Takashina.

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Takashina, K., Bessho, T., Mori, R. et al. MKC-231, a choline uptake enhancer: (3) mode of action of MKC-231 in the enhancement of high-affinity choline uptake. J Neural Transm 115, 1037–1046 (2008). https://doi.org/10.1007/s00702-008-0049-0

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  • DOI: https://doi.org/10.1007/s00702-008-0049-0

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