Récasens M, Sassetti I, Nourigat A, Sladeczek F, Bockaert J
Centre CNRS-INSERM de Pharmacologie-Endocrinologie, Montpellier, France.
Eur J Pharmacol. 1987 Sep 2;141(1):87-93. doi: 10.1016/0014-2999(87)90413-4.
The action of excitatory amino acids (EAA) on inositol phosphates (IPs) synthesis was examined in forebrain synaptoneurosomes of Long Evans rats (6-9 days old). Glutamate (GLU) (EC50: 23 microM) and quisqualate (QA) (EC50: 0.12 microM) enhanced IPs turnover. N-methyl-D-aspartate (NMDA) and kainate (KA) were less potent. The EAA-elicited IPs response was not blocked by tetrodotoxin (2 microM) or by the absence of Ca2+. This suggests that the activation of EAA receptors stimulates directly the phosphodiesterase responsible for phosphoinositide breakdown. The three main agonists (QA, KA and NMDA) tested in pairs, induced additive responses on IPs accumulation. In synaptoneurosomes prepared from adult rat, the relative responses to QA and GLU were dramatically reduced, whereas those to KA and NMDA remained unchanged. We concluded that GLU stimulates IPs formation mainly via a QA-like receptor subtype (AA2). This stimulation is transient and could play a key role during synaptogenesis. GLU also enhanced IPs accumulation via other receptor subtypes (probably of the NMDA- or AA1-like class).
在长 Evans 大鼠（6 - 9 日龄）的前脑突触神经小体中，研究了兴奋性氨基酸（EAA）对肌醇磷酸（IPs）合成的作用。谷氨酸（GLU）（半数有效浓度[EC50]：23 微摩尔）和quisqualate（QA）（EC50：0.12 微摩尔）增强了 IPs 的周转。N - 甲基 - D - 天冬氨酸（NMDA）和海人酸（KA）的效力较弱。EAA 引发的 IPs 反应不受河豚毒素（2 微摩尔）或无 Ca2+的阻断。这表明 EAA 受体的激活直接刺激了负责磷酸肌醇分解的磷酸二酯酶。成对测试的三种主要激动剂（QA、KA 和 NMDA）对 IPs 积累产生相加反应。在成年大鼠制备的突触神经小体中，对 QA 和 GLU 的相对反应显著降低，而对 KA 和 NMDA 的反应保持不变。我们得出结论，GLU 主要通过类似 QA 的受体亚型（AA2）刺激 IPs 形成。这种刺激是短暂的，可能在突触发生过程中起关键作用。GLU 还通过其他受体亚型（可能是类似 NMDA 或 AA1 的类型）增强 IPs 积累。
