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
- Received May 12, 2000.
- Accepted July 3, 2000.
-
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
-
This work was supported by National Institutes of Health Grants NS35891, GM07623-22, and MH34007.
- The American Society for Pharmacology and Experimental Therapeutics
MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|