RNA Editing of the Human Serotonin 5-HT2C Receptor Delays Agonist-Stimulated Calcium Release
- Departments of 1Pharmacology (R.D.P. and E.S.-B.) and 2Psychiatry (E.S.-B.) and the 3Center for Molecular Neuroscience (E.S.-B.), Vanderbilt University, Nashville, Tennessee
Abstract
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 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-HT2C receptors may produce distinct physiological responses within the central nervous system.
Footnotes
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Send reprint requests to: Elaine Sanders-Bush, Ph.D., Department of Pharmacology, Vanderbilt University, Nashville, TN 37232-6600. E-mail:elaine.bush{at}mcmail.vanderbilt.edu
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This work was supported by National Institutes of Health Grants NS35891, GM07623-22, and MH34007.
- Abbreviations:
- 5-HT2CR
- serotonin 5-HT2C receptor
- HBSS
- Hanks' balanced salt solution
- DOI
- (±)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane
- fura-2/AM
- fura-2 acetoxymethyl ester
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- Received May 12, 2000.
- Accepted July 3, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
