Messenger RNA Editing of the Human Serotonin 5-HT2C Receptor
| Autor: | Anne P. Marshall, Deborah S. Conklin, John P. Patterson, David P. Tran, Gerald J Jonak, Paul R. Hartig, Lawrence W. Fitzgerald, Carol M. Krause, Geeta Iyer |
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| Rok vydání: | 1999 |
| Předmět: |
Serotonin
Intrinsic activity Biology Transfection Polymerase Chain Reaction Cell Line Gene expression Receptor Serotonin 5-HT2C Animals Humans Protein Isoforms RNA Messenger Cloning Molecular Pharmacology Messenger RNA RNA Receptor editing Molecular biology Recombinant Proteins Rats Serotonin Receptor Agonists Cell biology 5-HT2C receptor Psychiatry and Mental health RNA editing Receptors Serotonin RNA Editing Serotonin Antagonists Synaptic signaling |
| Zdroj: | Neuropsychopharmacology. 21:82S-90S |
| ISSN: | 0893-133X |
| DOI: | 10.1016/s0893-133x(99)00004-4 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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