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Journal of Neural Transmission

, Volume 115, Issue 7, pp 1037–1046 | Cite as

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

  • Ken Takashina
  • Tomoko Bessho
  • Reiko Mori
  • Kunji Kawai
  • Junichi Eguchi
  • Ken-Ichi Saito
Alzheimer's Disease and Related Disorders - Original Article

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.

Keywords

MKC-231 AF64A High-affinity choline uptake (HACU) Acetyl choline HC-3 binding Choline transporter CHT1 

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Ken Takashina
    • 1
  • Tomoko Bessho
    • 1
  • Reiko Mori
    • 1
  • Kunji Kawai
    • 2
  • Junichi Eguchi
    • 1
  • Ken-Ichi Saito
    • 3
  1. 1.Pharmacology Department IV, Pharmacology Laboratory, Research DivisionMitsubishi Tanabe Pharma CorporationAoba-kuJapan
  2. 2.Lead Generation Research Department, Medicinal Chemistry Laboratory, Research DivisionMitsubishi Tanabe Pharma CorporationYokohamaJapan
  3. 3.Global Product Strategy DepartmentMitsubishi Tanabe CorporationTokyoJapan

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