Shinomura T, Nakao S, Adachi T, Shingu K
Department of Anesthesia, Kyoto University Hospital, Japan.
Anesth Analg. 1999 Jun;88(6):1401-5. doi: 10.1097/00000539-199906000-00037.
Glutamate is a major neural transmitter of noxious stimulation in the spinal cord. We measured glutamate release from rat spinal synaptoneurosomes by using an enzyme-linked fluorimetric assay. Glutamate was released from spinal cord synaptoneurosomes in response to the addition of 30 mM potassium chloride, 1 mM 4-aminopyridine, or 1 microM ionomycin in the presence of external calcium. There was less release of glutamate in the absence, versus the presence, of external calcium. Clonidine significantly reduced the level of glutamate released from the spinal cord synaptoneurosomes. Tetradecanoyl phorbol acetate, an activator of protein kinase C, enhanced glutamate release. Forskolin, a protein kinase A activator, had no effect on the glutamate efflux. Our data indicate that glutamate released in the spinal cord is dependent on protein kinase C but is independent of the protein kinase A pathway. They also suggest that the inhibition of glutamate release may be the underlying mechanism of antinociception by clonidine at the spinal cord level.
We demonstrated that synaptoneurosomes from rat spinal cord could release glutamate in response to depolarization. We showed that an activator of protein kinase C increased glutamate released from spinal cord synaptoneurosomes but that clonidine decreased it. Glutamate release may be one of the mechanisms of antinociception at the spinal cord level.
谷氨酸是脊髓中伤害性刺激的主要神经递质。我们使用酶联荧光分析法测量了大鼠脊髓突触体神经小体中谷氨酸的释放。在外部存在钙的情况下，加入30 mM氯化钾、1 mM 4-氨基吡啶或1 μM离子霉素会促使脊髓突触体神经小体释放谷氨酸。与存在外部钙相比，在没有外部钙的情况下谷氨酸释放较少。可乐定显著降低了脊髓突触体神经小体释放的谷氨酸水平。蛋白激酶C的激活剂十四酰佛波醇乙酸酯增强了谷氨酸的释放。蛋白激酶A激活剂福斯高林对谷氨酸外流没有影响。我们的数据表明，脊髓中释放的谷氨酸依赖于蛋白激酶C，但不依赖于蛋白激酶A途径。它们还表明，抑制谷氨酸释放可能是可乐定在脊髓水平产生抗伤害感受作用的潜在机制。
我们证明大鼠脊髓的突触体神经小体可响应去极化释放谷氨酸。我们表明蛋白激酶C的激活剂增加了脊髓突触体神经小体释放的谷氨酸，但可乐定使其减少。谷氨酸释放可能是脊髓水平抗伤害感受的机制之一。
