MKC-231, a choline uptake enhancer: (2) Effect on synthesis and release of acetylcholine in AF64A-treated rats
| Autor: | Ken Takashina, Jun-ichi Eguchi, Tomoko Bessho, Reiko Mori, Ken-Ichi Saito |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Microdialysis Aziridines In Vitro Techniques Hippocampal formation Pharmacology Tritium Hippocampus Choline In vivo medicine Animals Hippocampus (mythology) Drug Interactions Rats Wistar Biological Psychiatry Cholinesterase Analysis of Variance Dose-Response Relationship Drug biology Chemistry Radioimmunoassay Acetylcholine Rats Psychiatry and Mental health Neurology Potassium Quinolines Tacrine biology.protein Cholinergic Cholinesterase Inhibitors Neurology (clinical) Neuromuscular Blocking Agents Synaptosomes medicine.drug |
| Zdroj: | Journal of Neural Transmission. 115:1027-1035 |
| ISSN: | 1435-1463 0300-9564 |
| DOI: | 10.1007/s00702-008-0048-1 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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