Journal of Neural Transmission

, Volume 115, Issue 7, pp 1027–1035

MKC-231, a choline uptake enhancer: (2) Effect on synthesis and release of acetylcholine in AF64A-treated rats

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

Abstract

The effect of MKC-231 on acetylcholine (ACh) synthesis and release was studied in the hippocampus of normal and AF64A-treated rats. AF64A (3 nmol/brain, i.c.v.) produced significant reduction of high-affinity choline uptake (HACU) and high K+-induced ACh release in hippocampal synaptosomes. Treatments with MKC-231 (10−8 and 10−7 M) showed significant reverse of the decrease in both HACU and ACh release. In hippocampal slices superfused with choline-containing artificial cerebro-spinal fluid (ACSF), high K+-induced ACh release was gradually decreased by repeated alteration of resting and high K+ stimulations in AF64A-treated rats. However, addition of MKC-231 (10−8 to 10−7 M) in the superfusate reduces this decrease. In vivo microdialysis studies indicate MKC-231 (10 mg/kg, p.o.) significantly reversed reduction of basal ACh concentrations in AF64A-treated rats, measured by radioimmunoassay without a cholinesterase inhibitor in the perfusate. These results indicate MKC-231 improves AF64A-induced cholinergic hypofunction by enhancing HACU, subsequently facilitating ACh synthesis and release in vitro and in vivo.

Keywords

MKC-231 AF64A High-affinity choline uptake (HACU) Acetyl choline (ACh) Microdialysis Radioimmunoassay 

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Ken Takashina
    • 1
  • Tomoko Bessho
    • 1
  • Reiko Mori
    • 1
  • Junichi Eguchi
    • 1
  • Ken-Ichi Saito
    • 2
  1. 1.Pharmacology Department IV, Pharmacology Laboratory, Research Division 1000Mitsubishi Tanabe Pharma CorporationYokohamaJapan
  2. 2.Global Product Strategy DepartmentMitsubishi Tanabe Pharma CorporationTokyoJapan

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