Linked Life Data

19481555

Source:http://linkedlifedata.com/resource/pubmed/id/19481555

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-7-27
pubmed:abstractText
Several cytisine derivatives have been developed in the search for more selective drugs at nicotinic acetylcholine receptors (nAChR). Binding experiments in transfected cell lines showed that the iodination of cytisine in the position 3 of the pyridone ring increased potency at alpha7-nAChR and to a lesser extent at the alpha4beta2 subtypes, both of which are widely expressed in the brain. However, no in vivo studies have been published on this compound. Inhibition curves presented here using wild type, beta2, and beta4-null mutant mice confirm that 3-IC binds to alpha4beta2 *, alpha7 * and alpha3beta4 * receptors with higher affinity than cytisine (asterisk indicates the receptor may contain additional subunits, Lukas et al., 1999). Intraperitoneal injection of 3-iodocytisine (3-IC) induced considerable dose-dependent hypothermia in DBA/2J and C57BL/6J mice. This response was blocked by mecamylamine and partially inhibited by hexamethonium. beta4-null mice displayed significantly less 3-IC-induced hypothermia than wild-type mice, beta2-null mice were somewhat less affected than wild types, while responses of alpha7 *-null mice were similar to wild types. Mice treated chronically with 3-IC display a marked increase in alpha7 * and alpha4beta2 * binding sites determined by radioligand binding in membrane preparations from cerebral cortex and hippocampus. Quantitative autoradiographic analysis of 28 brain regions of mice treated with 3-IC was consistent with the membrane binding, detecting an increase of cytisine-sensitive [(125)I]epibatidine binding sites, while cytisine-resistant [(125)I]epibatidine sites were unchanged. [(125)I]alpha-Bungarotoxin binding sites also exhibited up-regulation. These results give a first evaluation of in vivo consequences of 3-IC as a potent agonist with marked effects on mice.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1873-7064
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
57
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
332-42
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
In vivo effects of 3-iodocytisine: pharmacological and genetic analysis of hypothermia and evaluation of chronic treatment on nicotinic binding sites.
pubmed:affiliation
Laboratory of Cellular and Molecular Biology and Neuroscience, Faculty of Sciences, University of Chile, Las Encinas 3370, Santiago, Chile.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural