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.
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Acknowledgments
The authors thank Prof. Koichiro Kawashima and Dr. Kazuko Fujimoto (Department of Pharmacology, Kyoritsu College of Pharmacy, Tokyo) for their invaluable technical advices and support for the microdialysis study and RIA assays for ACh.
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Takashina, K., Bessho, T., Mori, R. et al. MKC-231, a choline uptake enhancer: (2) Effect on synthesis and release of acetylcholine in AF64A-treated rats. J Neural Transm 115, 1027–1035 (2008). https://doi.org/10.1007/s00702-008-0048-1
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DOI: https://doi.org/10.1007/s00702-008-0048-1