Ivins K J, Molinoff P B
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia.
J Pharmacol Exp Ther. 1991 Oct;259(1):423-9.
P11 cells express a high density of 5-hydroxytryptamine2 (5-HT2) receptors coupled to phosphoinositide hydrolysis. The effect of exposure to 5-HT on the expression and function of 5-HT2 receptors in P11 cells was investigated. Exposure of P11 cells to 10 microM 5-HT for as short a time as 20 min led to a decrease in the ability of 5-HT to stimulate phosphoinositide hydrolysis. After 8 hr, phosphoinositide hydrolysis stimulated by 5-HT was greatly reduced or absent. Concentrations of 5-HT as low as 100 nM caused desensitization of phosphoinositide hydrolysis. Stimulation of phosphoinositide hydrolysis by 6-fluoronorepinephrine, an alpha-1 adrenergic agonist, was not affected by prior exposure of cells to 5-HT. Therefore, the decrease in response to 5-HT represented a selective, homologous desensitization of 5-HT2 receptor-mediated phosphoinositide hydrolysis. The density of 5-HT2 receptors in membranes prepared from P11 cells was measured using [125I]lysergic acid diethylamide. Exposure of P11 cells to 5-HT resulted in a decrease in the density of 5-HT2 receptors with no change in the affinity of the receptors for [125I]lysergic acid diethylamide. A decrease in the density of receptors was observed after exposure to 10 microM 5-HT for 1 hr, and after 24 hr the density of 5-HT2 receptors was approximately 30% of the original value. Down-regulation of 5-HT2 receptors in P11 cells may be involved in homologous desensitization of 5-HT2 receptor-mediated phosphoinositide hydrolysis.
P11细胞表达高密度的与磷酸肌醇水解偶联的5-羟色胺2（5-HT2）受体。研究了5-羟色胺（5-HT）暴露对P11细胞中5-HT2受体表达和功能的影响。将P11细胞暴露于10微摩尔/升的5-HT中，时间短至20分钟，就会导致5-HT刺激磷酸肌醇水解的能力下降。8小时后，5-HT刺激的磷酸肌醇水解大大降低或消失。低至100纳摩尔/升的5-HT浓度会导致磷酸肌醇水解脱敏。α-1肾上腺素能激动剂6-氟去甲肾上腺素刺激的磷酸肌醇水解不受细胞预先暴露于5-HT的影响。因此，对5-HT反应的降低代表了5-HT2受体介导的磷酸肌醇水解的选择性、同源脱敏。使用[125I]麦角酰二乙胺测量从P11细胞制备的膜中5-HT2受体的密度。P11细胞暴露于5-HT导致5-HT2受体密度降低，而受体对[125I]麦角酰二乙胺的亲和力没有变化。暴露于10微摩尔/升的5-HT 1小时后观察到受体密度降低，24小时后5-HT2受体密度约为原始值的30%。P11细胞中5-HT2受体的下调可能参与了5-HT2受体介导的磷酸肌醇水解的同源脱敏。
