PT  - JOURNAL ARTICLE
AU  - Gurevich, Ilona
AU  - Englander, Michael T.
AU  - Adlersberg, Mella
AU  - Siegal, Nathan B.
AU  - Schmauss, Claudia
TI  - Modulation of Serotonin 2C Receptor Editing by Sustained Changes in Serotonergic Neurotransmission
AID  - 10.1523/JNEUROSCI.22-24-10529.2002
DP  - 2002 Dec 15
TA  - The Journal of Neuroscience
PG  - 10529--10532
VI  - 22
IP  - 24
4099  - http://www.jneurosci.org/content/22/24/10529.short
4100  - http://www.jneurosci.org/content/22/24/10529.full
SO  - J. Neurosci.2002 Dec 15; 22
AB  - Serotonin 2C (5-HT2C) receptor pre-mRNA is a substrate for RNA editing enzymes that convert five adenosines (named A, B, C′, C, and D editing sites) to inosines. Editing of two of these sites (C′ and C) is crucial for decreasing the efficiency of the receptor to activate G-protein. Nucleotide sequence analysis of mouse forebrain neocortical 5-HT2C mRNA isoforms revealed that editing at these two sites is regulated in a serotonin-dependent manner. In serotonin-depleted mice, C′- and C-site editing is significantly decreased. This results in an increased expression of 5-HT2C mRNA isoforms encoding receptors with higher sensitivity to serotonin. In contrast, a 4 d treatment with the 5-HT2A/2C agonist (±)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane significantly increases the editing frequency at the C′ site and leads to increased expression of 5-HT2C mRNA isoforms encoding receptors that activate G-protein least efficiently. None of the drug treatments led to alterations in cytoplasmic 5-HT2C mRNA levels. These data indicate that editing of 5-HT2C pre-mRNA is a mechanism that retains basic response properties of 5-HT2Creceptors in the face of changing synaptic input to keep receptor activation within an optimal range for information processing.