Lerea L S, McNamara J O
Department of Medicine, Veterans Administration Medical Center, Durham, North Carolina.
Neuron. 1993 Jan;10(1):31-41. doi: 10.1016/0896-6273(93)90239-n.
N-Methyl-D-aspartate (NMDA) or non-NMDA receptor activation is sufficient to induce transcription of the immediate early gene c-fos in a calcium-requiring manner. We sought to determine whether the calcium-dependent mechanisms inducing c-fos transcription are identical following activation of these two receptor subtypes. We used in situ hybridization and fura-2 imaging to detect c-fos mRNA and intracellular calcium in individual dentate gyrus neurons maintained in vitro. Structurally distinct inhibitors of phospholipase A2 and cyclooxygenase abolished NMDA--but not kainic acid-induced increases of c-fos mRNA. Conversely, the calmodulin antagonist calmidazolium markedly inhibited kainic acid--but not NMDA-mediated increases of c-fos mRNA. We propose that the dissociation in the mechanisms transducing the calcium influx signals to the nucleus following NMDA and non-NMDA receptor activation is due to spatially distinct sites of calcium entry, resulting in activation of different enzymes located at distinct sites in the cell.
N-甲基-D-天冬氨酸（NMDA）或非NMDA受体激活足以以钙依赖的方式诱导即刻早期基因c-fos的转录。我们试图确定在这两种受体亚型激活后，诱导c-fos转录的钙依赖机制是否相同。我们使用原位杂交和fura-2成像来检测体外培养的单个齿状回神经元中的c-fos mRNA和细胞内钙。磷脂酶A2和环氧化酶的结构不同的抑制剂消除了NMDA诱导的而非海人酸诱导的c-fos mRNA增加。相反，钙调蛋白拮抗剂氯咪巴唑显著抑制海人酸介导的而非NMDA介导的c-fos mRNA增加。我们提出，NMDA和非NMDA受体激活后，将钙内流信号转导至细胞核的机制的分离是由于钙进入的空间不同位点，导致细胞中不同位点的不同酶被激活。
