Summary

Frequence, Function of Serotonin 2C Receptor mRNA Editing and its Relationship with Adenosine Deaminase during the Development of Rat and Primary Culture Cortical Cells

Serotonin 2C receptor (5-HT2CR) is one of among 14 kinds of serotonin receptor subtypes, have been reported to be involved in psychotic disorders. 5HT2CR mRNA receives editing at 5 nucleotide positions (named sites A – E) which are located inconsecutively on the sequence encoding the second intracellular loop of the receptor. Editing of 5-HT2CR mRNA involvesadenosine deaminase 1 and  -2 (ADAR-1 and -2 ) which catalyze editing at sites A and B and editing at sites C and D on 5-HT2CR mRNA, respectively. This study aimed, first, to clarify a physiological role of 5-HT2CR mRNA editing and second, to clarify if the changes in 5-HT2CR mRNA editing are involved in expression of ADAR-1 and -2. For the first aim, developmental changes in editing frequency of 5-HT2CR mRNA were investigated in the rat cerebral cortex and primary cultured cortical cells. The editing frequencies at sites A and B increased in parallel with the rat brain development and reached a plateau of 80 – 100% frequency at postnatal days 1 – 3.  Although editing frequency at site C was lower than those detected at other sites except site E during a developmental period, it reached the maximal value of 30% during a first 7-day period after birth and then decreased gradually to the negligible level at postnatal day 19 (PN49).  Site D showed almost constant susceptibility (about 60%) to editing, while no editing at site E was occurred. For the second aim, the expression of ADAR-1 and – was investigated. The results show that the expression levels of ADAR-2 mRNA increased during development, while the expression level of ADAR-1 mRNA was constant. These findings indicated that sites A – D have different susceptibility to editing and that the frequencies at these sites are not always constant during development. Since similar changes were observed in a primary cultured cell system, the system is useful to study the physiological significances of 5-HT2CR mRNA editing and drug effects on the editing during the development. Considering the data that the expression levels of these genes were not concomitant with the changes in editing of 5-HT2CR mRNA, other factor(s) beside ADARs may be involved in 5-HT2CR mRNA editing.

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