Balázs R, Hack N, Jørgensen O S
Netherlands Institute for Brain Research, Amsterdam.
Int J Dev Neurosci. 1990;8(4):347-59. doi: 10.1016/0736-5748(90)90068-d.
Differentiating granule cells develop survival requirements in culture which can be met by treatment with high K+ or N-methyl-D-aspartate (NMDA) and, according to our recent findings, also with low concentrations of kainic acid (KA, 50 microM). We have now attempted to elucidate the mechanism(s) underlying the trophic effect of KA. KA rescue of cells was completely suppressed by blockers of voltage-sensitive calcium channels, such as nifedipine in low concentrations (5 x 10(-7) M), indicating that the promotion of cell survival is mediated through the activation of these channels by membrane depolarization. Thus the trophic influences of KA and NMDA share a common mechanism, increased Ca2+ influx (albeit through different routes), a conclusion that is supported by the observation that the effects of these agonists at concentrations causing maximal promotion of cell survival were not additive. Interactive effects involving different classes of excitatory amino acid receptors were revealed by the potentiation of the KA rescue of cells by the NMDA receptor antagonists, 2-amino 5-phosphonovalerate (APV) or (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohept-5,10-imine hydrogen maleate (MK-801), which on their own failed to promote, but rather reduced cell survival. The potentiation of the KA effect by the competitive NMDA antagonist APV was counteracted by the weak NMDA agonist, quinolinic acid. These observations suggest that KA alone has both trophic and toxic effects, the latter being mediated secondarily through an NMDA-like glutamate receptor, which is distinct from the conventional NMDA, KA and quisqualate preferring subtypes.
分化的颗粒细胞在培养中产生生存需求，高钾离子（K⁺）或N-甲基-D-天冬氨酸（NMDA）处理可满足这些需求，并且根据我们最近的发现，低浓度的红藻氨酸（KA，50微摩尔）也可以。我们现在试图阐明KA营养作用的潜在机制。低浓度（5×10⁻⁷摩尔）的电压敏感性钙通道阻滞剂，如硝苯地平，可完全抑制KA对细胞的挽救作用，这表明细胞存活的促进是通过膜去极化激活这些通道介导的。因此，KA和NMDA的营养影响具有共同机制，即增加Ca²⁺内流（尽管通过不同途径），这一结论得到以下观察结果的支持：这些激动剂在引起细胞存活最大促进的浓度下的作用不是相加的。NMDA受体拮抗剂2-氨基-5-磷酸戊酸（APV）或（+）-5-甲基-10,11-二氢-5H-二苯并[a,d]环庚-5,10-亚胺氢马来酸盐（MK-801）增强了KA对细胞的挽救作用，揭示了涉及不同类型兴奋性氨基酸受体的相互作用，它们本身不能促进细胞存活，反而会降低细胞存活。竞争性NMDA拮抗剂APV对KA作用的增强被弱NMDA激动剂喹啉酸抵消。这些观察结果表明，单独的KA具有营养和毒性作用，后者继发于一种类似NMDA的谷氨酸受体介导，该受体不同于传统的NMDA、KA和quisqualate偏好亚型。
