Rhynchophylline and isorhynchophylline inhibit NMDA receptors expressed in Xenopus oocytes
Rhynchophylline and isorhynchophylline inhibit NMDA receptors expressed in Xenopus oocytes
复制标题
DOI：
10.1016/s0014-2999(02)02581-5
复制
发表时间：
2002-11-22
影响因子：
5
通讯作者：
Watanabe, H
中科院分区：
文献类型：
--
作者：
Kang, TH;Murakami, Y;Watanabe, H
钩藤碱和异钩藤碱是钩藤属植物中四环羟吲哚类生物碱的主要成分，长期以来一直被用作药用植物。在这项研究中，钩藤碱和isorhynchophylline离子型和代谢型谷氨酸受体介导的电流反应的影响进行了研究，使用非洲爪蟾卵母细胞注射总RNA从大鼠皮质或小脑。钩藤碱和异钩藤碱（1-100 μ M）本身不能诱导膜电流，但这些生物碱可逆地减少N-甲基-D-天冬氨酸（NMDA）诱导的电流，在浓度依赖性，但电压不依赖的方式。钩藤碱和异钩藤碱的IC_（50）值分别为43.2和48.3 μ M。记录介质中Ca ~（2+）被Ba ~（2+）取代后，钩藤碱和异钩藤碱对NMDA电流的抑制程度没有改变。相反，两种生物碱对离子型红藻氨酸型和（+/-）-α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）型谷氨酸受体或代谢型谷氨酸受体（1和5）（mGlu（1/5））介导的电流均无影响。Rhynchophylline和isorhynchophylline（30 μ M）显著降低NMDA和甘氨酸（NMDA受体的共激动剂）诱发的最大电流反应，但对NMDA和甘氨酸诱发电流的EC_（50）值和Hill系数无影响。这些生物碱没有表现出与NMDA受体上的多胺结合位点、Zn 2+位点、质子位点或氧化还原调节位点的相互作用。这些结果表明，钩藤碱和isorhynchophylline作为NMDA受体的非竞争性拮抗剂，这种性质可能有助于神经保护和抗惊厥活性的Uncaira物种植物提取物。(C)2002 Elsevier Science B. V.保留所有权利。
Rhynchophylline and isorhynchophylline are major tetracyclic oxindole alkaloid components of Uncaira species, which have been long used as medicinal plants. In this study, the effects of rhynchophylline and isorhynchophylline on the ionotropic and metabotropic glutamate receptor-mediated current responses were examined using Xenopus oocytes injected with total RNA prepared from rat cortices or cerebelli. Rhynchophylline and isorhynchophylline (1-100 muM) per se failed to induce membrane current, but these alkaloids reversibly reduced N-methyl-D-aspartate (NMDA)-induced current in a concentration-dependent but voltage-independent manner. The IC50 values of rhynchophylline and isorhynchophylline were 43.2 and 48.3 muM, respectively Substitution of Ba2+ for Ca2+ in the recording medium did not alter the extent of rhynchophylline- and isorhynchophylline-induced suppression of NMDA currents. In contrast, neither alkaloid had an effect on the currents mediated by ionotropic kainic acid-type and (+/-)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors or by the metabotropic glutamate receptor(1 and 5) (mGlu(1/5)). Rhynchophylline and isorhynchophylline (30 muM) significantly reduced the maximal current responses evoked by NMDA and glycine (a co-agonist of NMDA receptor), but had no effect on the EC50 values and Hill coefficients of NMDA and glycine for inducing currents. These alkaloids showed no interaction with the polyamine binding site, the Zn2+ site, proton site or redox modulatory site on the NMDA receptor. These results suggest that rhynchophylline and isorhynchophylline act as noncompetitive antagonists of the NMDA receptor and that this property may contribute to the neuroprotective and anticonvulsant activity of the Uncaira species plant extracts. (C) 2002 Elsevier Science B.V. All rights reserved.