PMID- 18461273
OWN - NLM
STAT- MEDLINE
DCOM- 20081105
LR  - 20220321
IS  - 0300-9564 (Print)
IS  - 0300-9564 (Linking)
VI  - 115
IP  - 7
DP  - 2008 Jul
TI  - MKC-231, a choline uptake enhancer: (3) Mode of action of MKC-231 in the 
      enhancement of high-affinity choline uptake.
PG  - 1037-46
LID - 10.1007/s00702-008-0049-0 [doi]
AB  - 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.
FAU - Takashina, Ken
AU  - Takashina K
AD  - Pharmacology Department IV, Pharmacology Laboratory, Research Division, 
      Mitsubishi Tanabe Pharma Corporation, 1000, Kamoshida-cho, Aoba-ku, Yokohama 
      227-0033, Japan. takashina.ken@mh.mt-pharma.co.jp
FAU - Bessho, Tomoko
AU  - Bessho T
FAU - Mori, Reiko
AU  - Mori R
FAU - Kawai, Kunji
AU  - Kawai K
FAU - Eguchi, Junichi
AU  - Eguchi J
FAU - Saito, Ken-Ichi
AU  - Saito K
LA  - eng
PT  - Journal Article
DEP - 20080507
PL  - Austria
TA  - J Neural Transm (Vienna)
JT  - Journal of neural transmission (Vienna, Austria : 1996)
JID - 9702341
RN  - 0 (Aziridines)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Neurotransmitter Uptake Inhibitors)
RN  - 0 (Quinolines)
RN  - 0 (choline transporter)
RN  - 10028-17-8 (Tritium)
RN  - 312-45-8 (Hemicholinium 3)
RN  - A668M9E227 (ethylcholine aziridinium)
RN  - N91BDP6H0X (Choline)
RN  - V6FL6O5GR7 (MKC 231)
SB  - IM
MH  - Animals
MH  - Aziridines/pharmacology
MH  - COS Cells
MH  - Cell Membrane/drug effects/metabolism
MH  - Chlorocebus aethiops
MH  - Choline/analogs & derivatives/*metabolism/pharmacology
MH  - Drug Interactions
MH  - Hemicholinium 3/pharmacology
MH  - Hippocampus/drug effects/ultrastructure
MH  - Male
MH  - Membrane Transport Proteins/genetics/metabolism
MH  - Neurotransmitter Uptake Inhibitors/pharmacology
MH  - Protein Binding/drug effects
MH  - Quinolines/*pharmacology
MH  - Radioligand Assay
MH  - Rats
MH  - Rats, Wistar
MH  - Synaptosomes/*drug effects/*metabolism
MH  - Transfection
MH  - Tritium/metabolism
EDAT- 2008/05/08 09:00
MHDA- 2008/11/06 09:00
CRDT- 2008/05/08 09:00
PHST- 2007/08/03 00:00 [received]
PHST- 2008/03/28 00:00 [accepted]
PHST- 2008/05/08 09:00 [pubmed]
PHST- 2008/11/06 09:00 [medline]
PHST- 2008/05/08 09:00 [entrez]
AID - 10.1007/s00702-008-0049-0 [doi]
PST - ppublish
SO  - J Neural Transm (Vienna). 2008 Jul;115(7):1037-46. doi: 
      10.1007/s00702-008-0049-0. Epub 2008 May 7.