Vol. 58, Issue 4, 859-862, October 2000

ACCELERATED COMMUNICATION
RNA Editing of the Human Serotonin 5-HT_2C Receptor Delays Agonist-Stimulated Calcium Release

Raymond D. Price and Elaine Sanders-Bush

Departments of Pharmacology (R.D.P. and E.S.-B.) and Psychiatry (E.S.-B.) and the Center for Molecular Neuroscience (E.S.-B.), Vanderbilt University, Nashville, Tennessee

RNA encoding the human 5-HT_2C 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 release. 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-HT_2C receptors may produce distinct physiological responses within the central nervous system.