Linked Life Data

20816767

Source:http://linkedlifedata.com/resource/pubmed/id/20816767

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2010-10-18
pubmed:abstractText
The ?7 nicotinic acetylcholine receptors (nAChRs) play an important role in the pathophysiology of neuropsychiatric diseases such as schizophrenia and Alzheimer's disease. However, there are currently no suitable small molecule radioligands for imaging ?7 nAChRs in the brain. In this study, we synthesized the novel radioligand [(125)I]4-iodophenyl 1,4-diazaicyclo[3.2.2]nonane-4-carboxylate ([(125)I]CHIBA-1006), a iodine-derivative of the selective ?7 nAChR agonist SSR180711, and studied the characterization of [(125)I]CHIBA-1006 binding to rat brain membranes. The assays of [(125)I]CHIBA-1006 binding to rat brain membranes were performed at 4°C. The presence of a single saturable high-affinity binding component for [(125)I]CHIBA-1006 in the rat brain was shown. Scatchard analysis revealed an apparent equilibrium dissociation constant (K(d)) of 88.2±21.4nM and a maximal number of binding sites (B(max)) of 65.4±6.8fmol/mg protein (mean±SEM, n=4). The specific binding of [(125)I]CHIBA-1006 was inhibited by a number of ?7 nAChR-selective ligands (e.g., unlabeled CHIBA-1006, SSR180711, CHIBA-1001, MG624 and A844606), suggesting a similarity among ?7 nAChR pharmacological profiles. In contrast, ?-bungarotoxin, MLA, and nicotine showed very weak affinity for [(125)I]CHIBA-1006 binding. The regional distribution of [(125)I]CHIBA-1006 binding to crude membranes from dissected regions of the rat brain was different from that of [(125)I]?-bungarotoxin binding, suggesting that [(125)I]CHIBA-1006 binding sites may not be identical to [(125)I]?-bungarotoxin binding sites in the rat brain. The present findings suggest that [(125)I]CHIBA-1006 would be a useful new small molecule radioligand for ?7 nAChRs in the brain.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1872-6240
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
11
pubmed:volume
1360
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
130-7
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Pharmacological characterization of [(125)I]CHIBA-1006 binding, a new radioligand for ?7 nicotinic acetylcholine receptors, to rat brain membranes.
pubmed:affiliation
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't