Regulation of 5-HT2A receptor mRNA in P11 cells

P11 cells were used as an in vitro model system to explore effects of exposure to 5-HT on levels of mRNA encoding 5-HT2A receptors. Exposure of cells to the agonist 5-HT resulted in a doubling of receptor mRNA levels. mRNA levels returned to control levels within 8-16 h. The stability of receptor mRNA transcripts was transiently increased, suggesting that a post-transcriptional process was responsible for the up-regulation of receptor mRNA. The 5-HT-induced increase in Levels on 5-HT2A receptor mRNA did not require de novo protein synthesis since the increase was not affected by prior treatment with the protein synthesis inhibitor cycloheximide. Results of studies in which the activity of protein kinase C was either increased with PMA or antagonized with bisindolylmaleimide indicated that protein phosphorylation was essential for increasing levels of 5-HT2A receptor mRNA. These findings suggest that PKC-dependent post-transcriptional and post-translational processes participate in regulating 5-HT2A receptor mRNA expression.