Linked Life Data

8765517

Source:http://linkedlifedata.com/resource/pubmed/id/8765517

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
1996-9-26
pubmed:abstractText
Alzheimer's disease is characterized by progressive cerebral cholinergic neuronal degeneration. Radiotracer analogs of benzovesamicol, which bind with high affinity to the vesamicol receptor located on the uptake transporter of acetylcholine storage vesicles, may provide an in vivo marker of cholinergic neuronal integrity. Five positional isomers of racemic iodobenzovesamicol (4'-, 5-, 6-, 7-, and 8-IBVM) were synthesized, exchange-labeled with iodine-125, and evaluated as possible in vivo markers for central cholinergic neurons. Only two isomers, 5-IBVM (5) and 6-IBVM (10), gave distribution patterns in mouse brain consistent with cholinergic innervation: striatum >> hippocampus > or = cortex > hypothalamus >> cerebellum. The 24-h tissue-to-cerebellum concentration ratios for 5-IBVM (5) were 3-4-fold higher for striatum, cortex, and hippocampus than the respective ratios for 6-IBVM (10). Neither 8-IBVM (16) nor 4'-IBVM (17) exhibited selective retention in any of the brain regions examined. In the heart, only 5-IBVM (5) exhibited an atria-to-ventricles concentration ratio consistent with high peripheral cholinergic neuronal selectivity. The 7-IBVM (14) isomer exhibited an anomalous brain distribution pattern, marked by high and prolonged retention in the five brain regions, most notably the cerebellum. This isomer was screened for binding in a series of 26 different biological assays; 7-IBVM (14) exhibited affinity only for the delta-receptor with an IC50 of approximately 30 nM. Drug-blocking studies suggested that brain retention of 7-IBVM (14) reflects high-affinity binding to both vesamicol and delta-receptors. Competitive binding studies using rat cortical homogenates gave IC50 values for binding to the vesamicol receptor of 2.5 nM for 5-IBVM (5), 4.8 nM for 6-IBVM (10), and 3.5 nM for 7-IBVM (14). Ex vivo autoradiography of rat brain after injection of (-)-5-[125I]IBVM ((-)-[125I]5) clearly delineated small cholinergic-rich areas such as basolateral amygdala, interpeduncular nucleus, and facial nuclei. Except for cortex, regional brain levels of (-)-5-[123I]IBVM ((-)-[123I]5) at 4 h exhibited a linear correlation (r2 = 0.99) with endogenous levels of choline acetyltransferase. Conclusion: Vesamicol receptor mapping of cholinergic nerve terminals in murine brain can be achieved with 5-IBVM (5) and less robustly with 6-IBVM (10), whereas the brain localization of 7-IBVM (14) reflects high-affinity binding to both vesamicol and delta-receptors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3331-42
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:8765517-Alzheimer Disease, pubmed-meshheading:8765517-Animals, pubmed-meshheading:8765517-Autoradiography, pubmed-meshheading:8765517-Binding, Competitive, pubmed-meshheading:8765517-Brain, pubmed-meshheading:8765517-Brain Mapping, pubmed-meshheading:8765517-Female, pubmed-meshheading:8765517-Guinea Pigs, pubmed-meshheading:8765517-Humans, pubmed-meshheading:8765517-Iodine Radioisotopes, pubmed-meshheading:8765517-Isomerism, pubmed-meshheading:8765517-Mice, pubmed-meshheading:8765517-Mice, Inbred Strains, pubmed-meshheading:8765517-Neuromuscular Depolarizing Agents, pubmed-meshheading:8765517-Neurons, pubmed-meshheading:8765517-Organ Specificity, pubmed-meshheading:8765517-Piperidines, pubmed-meshheading:8765517-Rats, pubmed-meshheading:8765517-Rats, Sprague-Dawley, pubmed-meshheading:8765517-Receptors, Cholinergic, pubmed-meshheading:8765517-Tetrahydronaphthalenes
pubmed:year
1996
pubmed:articleTitle
Vesamicol receptor mapping of brain cholinergic neurons with radioiodine-labeled positional isomers of benzovesamicol.
pubmed:affiliation
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0552, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.