Linked Life Data

10432493

Source:http://linkedlifedata.com/resource/pubmed/id/10432493

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2 Suppl
pubmed:dateCreated
1999-9-17
pubmed:abstractText
RNA encoding the rat serotonin 5-HT2C receptor undergoes editing whereby one to four adenosines are converted to inosines. This conversion can change up to three codons out of a stretch of five in the second intracellular loop of the receptor. RNA editing of the rat 5-HT2C receptor that changes all three codons was shown previously to alter intracellular signaling by 5-HT without changing its receptor-binding affinity. We analyzed 5-HT2C receptor editing in human brain and hypothalamic RNA samples and confirmed that all four adenosine editing sites observed in rat were also present in human samples. Additionally, we identified a novel editing site in the middle edited codon that extends the repertoire of 5-HT2C receptors by six additional protein isoforms. We observed that editing reduces both the binding affinity and functional potency of agonists for recombinant human 5-HT2C receptor isoforms. This effect on binding affinity was proportional to the agonist's intrinsic activity, with full agonists most affected, and antagonists showing no effect. These data suggest that RNA editing may alter coupling energetics within the ternary complex, thereby altering agonist binding affinities, G protein coupling, and functional responses. RNA editing may thus provide a novel mechanism for regulating 5-HT synaptic signaling and plasticity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0893-133X
pubmed:author
pubmed:issnType
Print
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
82S-90S
pubmed:dateRevised
2011-5-18
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Messenger RNA editing of the human serotonin 5-HT2C receptor.
pubmed:affiliation
CNS Diseases Research, DuPont Pharmaceuticals Research Laboratories, Wilmington, Delaware 19880, USA.
pubmed:publicationType
Journal Article