Linked Life Data

20881005

Source:http://linkedlifedata.com/resource/pubmed/id/20881005

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-12-15
pubmed:abstractText
Genomic studies have identified a D398N variation in the ?5 subunit of nicotinic acetylcholine receptors (AChRs) that increases risk of nicotine dependence and lung cancer. (?4?2)??5 AChRs are a significant brain presynaptic subtype in brain. Their high sensitivity to activation by nicotine and high Ca²+ permeability give them substantial functional impact. ?3?4* and ?3?2* AChRs are predominant postsynaptic AChRs in the autonomic nervous system, but rare in brain. The amino acid 398 of ?5 is located in the large cytoplasmic domain near the amphipathic ? helix preceding the M4 transmembrane domain. These helices have been shown to influence AChR conductance by forming portals to the central channel. We report that ?5 Asn 398 lowers Ca²+ permeability and increases short-term desensitization in (?4?2)??5 but not in (?3?4)??5 or (?3?2)??5 AChRs. This suggests that a positive allosteric modulator would augment nicotine replacement therapy for those with this risk variant. ?5 D398N variation does not alter sensitivity to activation. The high sensitivity to activation and desensitization of (?4?2)??5 AChRs by nicotine results in a narrow concentration range in which activation and desensitization curves overlap. This region centers on 0.2 ?M nicotine, a concentration typically sustained in smokers. This concentration would desensitize 60% of these AChRs and permit smoldering activation of the remainder. The low sensitivity to activation and desensitization of (?3?4)??5 AChRs by nicotine results in a broad region of overlap centered near 10 ?M. Thus, at the nicotine concentrations in smokers, negligible activation or desensitization of this subtype would occur.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1521-0111
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
79
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
119-25
pubmed:dateRevised
2011-1-14
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Acetylcholine receptor (AChR) ?5 subunit variant associated with risk for nicotine dependence and lung cancer reduces (?4?2)??5 AChR function.
pubmed:affiliation
Department of Neuroscience, University of Pennsylvania Medical School, Philadelphia, Pennsylvania, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, N.I.H., Extramural