Larsson C, Simonsson P, Caron M, Alling C
Department of Medical Neurochemistry, Lund University Hospital, Sweden.
J Pharmacol Exp Ther. 1996 Jul;278(1):313-9.
The effect of long-term ethanol exposure on muscarinic receptors was investigated in human neuroblastoma SH-SY5Y cells. Exposure to 100 mM ethanol for 4 days enhanced both peak and steady-state levels of carbachol-stimulated inositol 1,4,5-bisphosphate increase. An ethanol concentration of 50 mM was sufficient for an enhancement of this event. The carbachol-stimulated decrease in [3H]inositol-labeled [3H]phosphatidylnositol 4,5-bisphosphate and increase [3H]inositol trisphosphate and [3H]inositol bisphosphate were also potentiated in ethanol-treated cells, which demonstrated that the receptor-stimulated activation of phospholipase C is augmented. Experiments with pirenzepine showed that carbachol-stimulated inositol 1,4,5-trisphosphate increase is mediated via M1 receptors both in ethanol-treated and control cells. Ethanol exposure for 2 or 4 days also caused an increase in [3H]N-methylscopolamine and [3H]quinuclidinyl benzilate binding sites and elevation of [3H]pirenzepine binding, which indicated that the number of muscarinic M1 receptors is increased in ethanol-treated SH-SY5Y cells. These results demonstrate that long-term exposure to ethanol potentiates muscarinic M1 receptor-stimulated activation of phospholipase C in SH-SY5Y cells. This is likely to be explained by an increased number of muscarinic M1 receptors.
在人神经母细胞瘤SH-SY5Y细胞中研究了长期乙醇暴露对毒蕈碱受体的影响。用100 mM乙醇处理4天可增强卡巴胆碱刺激的肌醇1,4,5-二磷酸增加的峰值和稳态水平。50 mM的乙醇浓度足以增强此效应。在乙醇处理的细胞中，卡巴胆碱刺激的[3H]肌醇标记的[3H]磷脂酰肌醇4,5-二磷酸减少以及[3H]肌醇三磷酸和[3H]肌醇二磷酸增加也得到增强，这表明受体刺激的磷脂酶C激活增强。用哌仑西平进行的实验表明，在乙醇处理的细胞和对照细胞中，卡巴胆碱刺激的肌醇1,4,5-三磷酸增加均通过M1受体介导。乙醇暴露2天或4天还导致[3H]N-甲基东莨菪碱和[3H]喹核醇基苯甲酸酯结合位点增加以及[3H]哌仑西平结合升高，这表明在乙醇处理的SH-SY5Y细胞中毒蕈碱M1受体数量增加。这些结果表明，长期暴露于乙醇可增强SH-SY5Y细胞中毒蕈碱M1受体刺激的磷脂酶C激活。这可能是由于毒蕈碱M1受体数量增加所致。
