Price R D, Sanders-Bush E
Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232-6600, USA.
Mol Pharmacol. 2000 Oct;58(4):859-62. doi: 10.1124/mol.58.4.859.
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 (EC(50) values: hINI, 2.2 nM; hVSV, 15 nM; hVGV, 49 nM). Additionally, the hVGV receptor showed a blunted and delayed Ca(2+) peak compared with the hINI or hVSV receptor isoforms. These distinctions in agonist-induced Ca(2+) release imply that edited 5-HT(2C) receptors may produce distinct physiological responses within the central nervous system.
编码人5-羟色胺（5-HT）2C受体的RNA在假定的第二个细胞内环的五个位置经历腺苷到肌苷的RNA编辑事件，同时受体与G蛋白的偶联相应减少。在稳定表达未编辑的人INI（hINI）或编辑后的hVSV或hVGV变体的NIH-3T3成纤维细胞中检测了激动剂刺激的钙释放。我们假设不同的受体亚型会表现出激动剂诱导的钙释放动力学改变。这三种亚型在引发钙释放的激动剂浓度-反应曲线上显示出向右的偏移（半数有效浓度值：hINI为2.2 nM；hVSV为15 nM；hVGV为49 nM）。此外，与hINI或hVSV受体亚型相比，hVGV受体显示出钝化且延迟的细胞内钙离子（[Ca²⁺]i）峰值。激动剂诱导的细胞内钙离子（[Ca²⁺]i）释放的这些差异意味着编辑后的5-HT2C受体可能在中枢神经系统内产生不同的生理反应。
