Rahman S, Neuman R S
Faculty of Medicine, Memorial University, St. John's Newfoundland, Canada.
Eur J Pharmacol. 1993 Jul 20;238(2-3):173-80. doi: 10.1016/0014-2999(93)90845-9.
Desensitization of serotonin 5-HT2 receptor-mediated enhancement of the N-methyl-D-aspartate (NMDA) depolarization was studied in rat cortical neurons. Serotonin and (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) induced long term desensitization. Staurosporine, a nonspecific protein kinase C inhibitor, potentiated the serotonin and DOI facilitation, suggesting acute desensitization was operative. In the case of DOI, long term desensitization was prevented by staurosporine. Activators of protein kinase C abolished the serotonin facilitation, an action prevented by staurosporine. Concanavalin A potentiated the facilitation at 100 microM, but not 30 microM serotonin, suggesting these receptors undergo dose dependent internalization. Calmodulin antagonists prevent long term desensitization induced by serotonin. The depolarization induced by NMDA alone was not altered by staurosporine, protein kinase C activators, concanavalin A or calmodulin antagonists. Serotonin at 100 microM, but not 30 microM, induced heterologous desensitization of phenylephrine and carbachol induced facilitation of the NMDA depolarization. We conclude that serotonin 5-HT2 receptors both induce and undergo several forms of desensitization.
在大鼠皮层神经元中研究了5-羟色胺5-HT2受体介导的N-甲基-D-天冬氨酸（NMDA）去极化增强的脱敏作用。5-羟色胺和（±）-1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷（DOI）诱导长期脱敏。星形孢菌素，一种非特异性蛋白激酶C抑制剂，增强了5-羟色胺和DOI的促进作用，提示急性脱敏起作用。就DOI而言，星形孢菌素可预防长期脱敏。蛋白激酶C激活剂消除了5-羟色胺的促进作用，星形孢菌素可阻止此作用。伴刀豆球蛋白A在100μM时增强促进作用，但在5-羟色胺为30μM时则不然，提示这些受体发生剂量依赖性内化。钙调蛋白拮抗剂可预防5-羟色胺诱导的长期脱敏。单独的NMDA诱导的去极化不受星形孢菌素、蛋白激酶C激活剂、伴刀豆球蛋白A或钙调蛋白拮抗剂的影响。100μM而非30μM的5-羟色胺诱导去甲肾上腺素和卡巴胆碱诱导的NMDA去极化促进作用的异源脱敏。我们得出结论，5-羟色胺5-HT2受体既能诱导又能经历几种形式的脱敏。
