RNA editing of the human serotonin 5-HT2C receptor. alterations in suicide and implications for serotonergic pharmacotherapy.

Niswender CM, Herrick-Davis K, Dilley GE, Meltzer HY, Overholser JC, Stockmeier CA, Emeson RB, Sanders-Bush E
Neuropsychopharmacology. 2001 24 (5): 478-91

PMID: 11282248 · DOI:10.1016/S0893-133X(00)00223-2

RNA encoding the human serotonin 5-HT2C receptor (5-HT(2C)R) undergoes adenosine-to-inosine RNA editing events at five positions, resulting in an alteration of amino acids in the second intracellular loop. Several edited 5-HT(2C)Rs possess a reduced G-protein coupling efficiency compared to the completely non-edited isoform. The current studies show that the efficacy of the hallucinogenic drug lysergic acid diethylamide and of antipsychotic drugs is regulated by RNA editing, suggesting that alterations in editing efficiencies or patterns might result in the generation of a 5-HT(2C)R population differentially responsive to serotonergic drugs. An examination of the efficiencies of RNA editing of the 5-HT(2C)R in prefrontal cortex of control individuals vs. subjects diagnosed with schizophrenia or major depressive disorder revealed no significant differences in RNA editing among the three populations. However, subjects who had committed suicide (regardless of diagnosis) exhibited a statistically significant elevation of editing at the A-site, which is predicted to change the amino acid sequence in the second intracellular loop of the 5-HT(2C)R. These findings suggest that alterations in RNA editing may contribute to or complicate therapy in certain psychiatric disorders.

MeSH Terms (21)

Adult Amino Acid Sequence Animals Antipsychotic Agents COS Cells Depressive Disorder Female Humans Lysergic Acid Diethylamide Male Middle Aged Prefrontal Cortex Protein Isoforms Receptor, Serotonin, 5-HT2C Receptors, Serotonin RNA, Messenger RNA Editing Schizophrenia Serotonin Serotonin Receptor Agonists Suicide

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