Larson A A, Beitz A J
Department of Veterinary Biology, University of Minnesota, St. Paul 55108.
J Neurosci. 1988 Oct;8(10):3822-6. doi: 10.1523/JNEUROSCI.08-10-03822.1988.
Strychnine poisoning leads to seizures that have traditionally been attributed to competitive antagonism of glycine receptors in the spinal cord. Although glycine is thought to act as an inhibitory neurotransmitter, a strychnine-insensitive glycine (Gly2) receptor has been recently described in cultured mouse neurons that is thought to be allosterically linked to the excitatory amino acid NMDA receptor. The present study demonstrates that intrathecally administered glycine, in contrast to other putative inhibitory transmitters, potentiates rather than inhibits strychnine-induced convulsions in mice. The seizure-potentiating effects of glycine are blocked by aminophosphonovaleric acid, an NMDA antagonist. In addition, in animals pretreated with a subconvulsive dose of strychnine to block strychnine-sensitive glycine receptors (Gly1), glycine enhances, rather than inhibits, NMDA-induced convulsions. Together, these results indicate that the seizure-potentiating effects of glycine involve activation of NMDA receptors. This study provides the first evidence that glycine is capable of modulating the activity of NMDA receptors in the spinal cords of adult animals. In light of the elevated concentrations of glycine found in epileptogenic brain foci, these data also suggest that glycine may be a positive modulator in the production of epileptic seizures.
士的宁中毒会引发惊厥，传统上认为这是由于脊髓中甘氨酸受体的竞争性拮抗作用所致。尽管甘氨酸被认为是一种抑制性神经递质，但最近在培养的小鼠神经元中发现了一种对士的宁不敏感的甘氨酸（Gly2）受体，该受体被认为与兴奋性氨基酸NMDA受体存在变构联系。本研究表明，与其他假定的抑制性递质相反，鞘内注射甘氨酸会增强而非抑制小鼠的士的宁诱导惊厥。甘氨酸的惊厥增强作用可被NMDA拮抗剂氨基磷酸戊酸阻断。此外，在用亚惊厥剂量的士的宁预处理以阻断对士的宁敏感的甘氨酸受体（Gly1）的动物中，甘氨酸增强而非抑制NMDA诱导的惊厥。总之，这些结果表明甘氨酸的惊厥增强作用涉及NMDA受体的激活。本研究提供了首个证据，证明甘氨酸能够调节成年动物脊髓中NMDA受体的活性。鉴于在致痫性脑病灶中发现甘氨酸浓度升高，这些数据还表明甘氨酸可能是癫痫发作产生中的一种正性调节剂。
