RNA editing of the human serotonin 5-HT2C receptor delays agonist-stimulated calcium release

RNA encoding the human 5-HT2C receptor undergoes adenosine-to-inosine RNA editing events at five positions in the putative second intracellular loop, with a corresponding reduction in receptor/G-protein coupling. Agonist-stimulated calcium release was examined in NIH-3T3 fibroblasts stably expressing the nonedited human INI (hINI) or the edited hVSV or hVGV variants. We hypothesized that different receptor isoforms would show altered dynamics of agonist-induced calcium re-lease. The three isoforms showed a rightward shift in agonist concentration-response curves for eliciting calcium release (EC50 values: hINI, 2.2 nM; hVSV, 15 nM; hVGV, 49 nM). Additionally, the hVGV receptor showed a blunted and delayed [Ca2+](i) peak compared with the hINI or hVSV receptor isoforms. These distinctions in agonist-induced [Ca2+](i) release imply that edited 5-HT2C receptors may produce distinct physiological responses within the central nervous system.