MKC-231, a choline uptake enhancer: (3) mode of action of MKC-231 in the enhancement of high-affinity choline uptake
| Autor: | Ken-Ichi Saito, Kunji Kawai, Ken Takashina, Tomoko Bessho, Reiko Mori, Jun-ichi Eguchi |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Neurotransmitter Uptake Inhibitors Aziridines Pharmacology Transfection Tritium Hippocampus Choline Radioligand Assay chemistry.chemical_compound Hemicholinium-3 Chlorocebus aethiops medicine Animals Drug Interactions Rats Wistar Mode of action Biological Psychiatry Cell Membrane Membrane Transport Proteins Transporter Hemicholinium 3 Rats Choline transporter Psychiatry and Mental health Neurology chemistry Biochemistry COS Cells Quinolines Cholinergic Neurology (clinical) Acetylcholine Protein Binding Synaptosomes medicine.drug |
| Zdroj: | Journal of Neural Transmission. 115:1037-1046 |
| ISSN: | 1435-1463 0300-9564 |
| Popis: | 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 Vmax of HACU and Bmax 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. |
| Databáze: | OpenAIRE |
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