Polc P, Haefely W
Naunyn Schmiedebergs Arch Pharmacol. 1977 Nov;300(3):199-203. doi: 10.1007/BF00500961.
Kainic acid (a rigid conformational analogue of glutamate), N-methyl-D-aspartate (the methylated derivative of aspartate), and (--)-nuciferine (an aporphine alkaloid with a depressant effect on glutamate-induced neuronal firing), which, so far, have been examined in microiontophoretic studies, were investigated in spinal cats for their effects on some spinal cord activities after intravenous injections. At low doses, kainic acid (0.3 mg kg-1) enhanced segmental monosynaptic but not polysynaptic ventral root reflexes and increased the excitability of motoneurones, whereas N-methyl-D-aspartate (3 mg kg-1) facilitated polysynaptic but not monosynaptic reflexes. Higher doses of the two amino acids depolarized motoneurones and primary afferent endings, enhanced monosynaptic reflexes and depressed polysynaptic reflexes. (--)-Nuciferine (1--10 mg kg-1) depressed monosynaptic but not polysynaptic ventral root reflexes in a dose-dependent manner and antagonized the effects of kainic acid but not of N-methyl-D-aspartate on the spinal cord. The results are consistent with the hypothetical excitatory transmitter role of glutamate in primary afferents and of aspartate in excitatory spinal cord interneurones; the findings also suggest that (--)-nuciferine may be used as a systemically effective, rather selective blocker of central glutamate receptors.
海藻酸(谷氨酸的一种刚性构象类似物)、N-甲基-D-天冬氨酸(天冬氨酸的甲基化衍生物)以及(--)-荷叶碱(一种对谷氨酸诱导的神经元放电有抑制作用的阿朴啡生物碱),到目前为止,已在微离子电泳研究中进行了检测,此次在脊髓猫身上研究了它们静脉注射后对脊髓某些活动的影响。低剂量时,海藻酸(0.3毫克/千克)增强节段性单突触而非多突触腹根反射,并增加运动神经元的兴奋性,而N-甲基-D-天冬氨酸(3毫克/千克)促进多突触而非单突触反射。两种氨基酸的高剂量使运动神经元和初级传入末梢去极化,增强单突触反射并抑制多突触反射。(--)-荷叶碱(1 - 10毫克/千克)以剂量依赖方式抑制单突触而非多突触腹根反射,并拮抗海藻酸对脊髓的作用,但不拮抗N-甲基-D-天冬氨酸对脊髓的作用。这些结果与谷氨酸在初级传入神经中作为假设的兴奋性递质以及天冬氨酸在兴奋性脊髓中间神经元中作为假设的兴奋性递质的作用相一致;研究结果还表明,(--)-荷叶碱可用作一种全身有效的、相当有选择性的中枢谷氨酸受体阻滞剂。