Linked Life Data

18023504

Source:http://linkedlifedata.com/resource/pubmed/id/18023504

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2008-3-31
pubmed:abstractText
Mice deficient for acetylcholinesterase (AChE) have strongly increased extracellular levels of acetylcholine (ACh) in the dorsal hippocampus [Hartmann, J., Kiewert, C., Duysen, E.G., Lockridge, O., Greig, N.H., Klein, J., 2007. Excessive hippocampal acetylcholine levels in acetylcholinesterase-deficient mice are moderated by butyrylcholinesterase activity. J. Neurochem. 100, 1421-1429]. Using microdialysis, we found that increased ACh levels are accompanied by decreased levels of extracellular choline which were 1.60 microM in AChE-deficient mice and 4.36 microM in wild-type mice. Addition of choline (10 microM) to the perfusion fluid, while ineffective in wild-type animals, more than doubled extracellular ACh levels in AChE-deficient mice. High-affinity choline uptake (HACU), as measured ex vivo in corticohippocampal synaptosomes, was more than doubled in AChE-deficient mice. Inhibition of HACU by hemicholinium-3 (HC-3) in vivo reduced extracellular levels of ACh by 60% in wild-type mice but by more than 90% in AChE-deficient mice. Decreased ACh levels caused by infusion of HC-3 or tetrodotoxin (TTX) were accompanied by increased levels of free choline. Infusion of scopolamine (1 microM) caused a fivefold increase of ACh levels in wild-type animals but only a 50% increase in AChE-deficient mice. In conclusion, absence of AChE causes dynamic changes in the ratio of choline to ACh. High levels of extracellular ACh are accompanied by reduced levels of extracellular choline, and ACh release becomes strongly dependent on choline availability. Similar changes may take place in patients chronically exposed to AChE inhibitors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0197-0186
pubmed:author
pubmed:issnType
Print
pubmed:volume
52
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
972-8
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:18023504-Acetylcholine, pubmed-meshheading:18023504-Acetylcholinesterase, pubmed-meshheading:18023504-Animals, pubmed-meshheading:18023504-Choline, pubmed-meshheading:18023504-Cholinergic Antagonists, pubmed-meshheading:18023504-Down-Regulation, pubmed-meshheading:18023504-Extracellular Fluid, pubmed-meshheading:18023504-Female, pubmed-meshheading:18023504-Hemicholinium 3, pubmed-meshheading:18023504-Hippocampus, pubmed-meshheading:18023504-Male, pubmed-meshheading:18023504-Mice, pubmed-meshheading:18023504-Mice, Knockout, pubmed-meshheading:18023504-Microdialysis, pubmed-meshheading:18023504-Neurotransmitter Uptake Inhibitors, pubmed-meshheading:18023504-Presynaptic Terminals, pubmed-meshheading:18023504-Scopolamine Hydrobromide, pubmed-meshheading:18023504-Seizures, pubmed-meshheading:18023504-Sodium Channel Blockers, pubmed-meshheading:18023504-Synaptic Transmission
pubmed:year
2008
pubmed:articleTitle
Choline availability and acetylcholine synthesis in the hippocampus of acetylcholinesterase-deficient mice.
pubmed:affiliation
Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Science Center, Amarillo, TX, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural