Cellular mechanisms of serotonin 5-HT2A receptor-mediated cGMP formation: the essential role of glutamate.
Cellular mechanisms of serotonin 5-HT2A receptor-mediated cGMP formation: the essential role of glutamate.
复制标题
血清素 5-HT2A 受体介导的 cGMP 形成的细胞机制：谷氨酸的重要作用。
DOI：
10.1016/j.brainres.2004.01.014
复制
发表时间：
2004
期刊：
影响因子：
2.9
通讯作者：
Rabin,RichardA
中科院分区：
文献类型：
--
作者：
Regina,MeredithJ;Bucelli,RobertC;Winter,JerroldC;Rabin,RichardA
本研究探讨了5-羟色胺2A(5-HT2A)受体激活增加大鼠额叶脑片环鸟苷一磷酸(CGMP)产生的机制。与大脑皮层切片的结果相反，刺激稳定表达5-羟色胺受体的细胞中的5-HT2A受体不会改变cGMP水平。在皮层脑片中，5-HT2A/2C受体激动剂2，5-二甲氧基-4-甲基苯丙胺(DOM)对cGMP形成的刺激作用可被破伤风毒素阻断，破伤风毒素是一种阻止囊泡神经递质释放的物质。然而，这种刺激并没有被河豚毒素改变，河豚毒素是一种抑制去极化诱导的神经递质释放的药物。加入N-甲基-d-天冬氨酸(NMDA)受体拮抗剂d-AP-7，但不加入AMPA/海人藻酸受体拮抗剂CNQX，可完全抑制DOM介导的cGMP在脑片中的产生。联合应用最大有效浓度的NMDA和DOM比单独使用任何一种药物都能更大地增加cGMP的含量。本研究表明，5-HT2A受体并不直接刺激cGMP的形成，而是依赖于细胞外谷氨酸激活NMDA受体。结果表明，5-HT2A受体介导的cGMP的产生至少部分归因于增强NMDA受体介导的cGMP的形成。
The current study explores the mechanisms by which activation of serotonin2A(5-HT2A) receptors increase production of cyclic guanosine monophosphate (cGMP) in slices of rat frontal cortex. Contrary to results in cortical slices, stimulation of 5-HT2Areceptors in cells stably expressing this serotonin receptor did not alter cGMP levels. In cortical slices, stimulation of cGMP formation by 2,5-dimethoxy-4-methylamphetamine (DOM), a 5-HT2A/2Creceptor agonist, was blocked by tetanus toxin, a substance that prevents vesicular neurotransmitter release. However, this stimulation was not altered by tetrodotoxin, an agent that inhibits depolarization-induced neurotransmitter release. Addition of an N-methyl-d-aspartate (NMDA) receptor antagonist, d-AP-7, but not of an AMPA/kainate receptor antagonist CNQX, completely inhibited DOM-mediated cGMP production in the slices. Combined application of maximally effective concentrations of NMDA and DOM elicited a greater increase in cGMP content than either drug alone. The present study shows that 5-HT2Areceptors do not directly stimulate cGMP formation, but rather that 5-HT2Areceptor-mediated cGMP production is dependent on extracellular glutamate activating NMDA receptors. The results indicate that 5-HT2Areceptor-mediated cGMP production could be at least partially attributed to potentiation of NMDA receptor-mediated cGMP formation.