Morari M, Calo G, Ferraro L, Fabrizi A, Acciarri N, Piazza G, Bianchi C, Beani L
Institute of Pharmacology, University of Ferrara, Italy.
Neurochem Int. 1995 Jan;26(1):77-83. doi: 10.1016/0197-0186(94)00099-g.
The effect of excitatory amino acids (EAA) on phosphatidylinositol (PI) turnover in human cerebral cortical slices was investigated. Trans-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) increased inositol phosphate (IP) formation in the 1-1000 microM range. Quisqualic acid (QA) was maximally effective at 10-100 microM, showing an inverse correlation between concentration and effect in the 100-1000 microM range. The glutamate metabotropic receptor antagonist 2-amino-3-phosphonopropionic acid (AP3), the ionotropic non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and the NMDA channel blocker dizolcipine (MK-801) failed to prevent the PI response to ACPD (1000 microM). However, CNQX (100 microM) modified the concentration-response curve of QA reducing the effect of QA 10 microM by approx. 50% and enhancing that of QA 1000 microM by 2-fold. In addition, CNQX (100 microM) together with MK-801 (100 microM) unmasked the ability of L-glutamate (L-GLU) 3000 microM to stimulate PI turnover. The effect of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) on the EAA-induced PI turnover was also studied. AMPA (0.1-1 microM) potentiated the response to submaximal (30 microM) ACPD and (1 microM) QA concentrations. However, higher AMPA concentrations (10 microM) failed to synergize with ACPD 30 microM and, in addition, inhibited the PI turnover maximally stimulated by QA 10 microM. These results further support the presence of the glutamate metabotropic receptor in the human neocortex. In addition, they show the occurrence of a concentration-related dual interaction between AMPA and glutamate metabotropic receptor activation in the IP formation in this brain area.
研究了兴奋性氨基酸（EAA）对人脑皮质切片中磷脂酰肌醇（PI）周转的影响。反式-1-氨基环戊烷-1,3-二羧酸（ACPD）在1-1000微摩尔范围内增加了肌醇磷酸（IP）的形成。喹啉酸（QA）在10-100微摩尔时效果最佳，在100-1000微摩尔范围内浓度与效果呈负相关。谷氨酸代谢型受体拮抗剂2-氨基-3-膦酰丙酸（AP3）、离子型非NMDA受体拮抗剂6-氰基-7-硝基喹喔啉-2,3-二酮（CNQX）和NMDA通道阻滞剂地佐环平（MK-801）未能阻止PI对ACPD（1000微摩尔）的反应。然而，CNQX（100微摩尔）改变了QA的浓度-反应曲线，使10微摩尔QA的效果降低了约50%，并使1000微摩尔QA的效果增强了2倍。此外，CNQX（100微摩尔）与MK-801（100微摩尔）共同揭示了3000微摩尔L-谷氨酸（L-GLU）刺激PI周转的能力。还研究了α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）对EAA诱导的PI周转的影响。AMPA（0.1-1微摩尔）增强了对亚最大浓度（30微摩尔）ACPD和（1微摩尔）QA的反应。然而，更高浓度的AMPA（10微摩尔）未能与30微摩尔ACPD协同作用，此外，还最大程度地抑制了10微摩尔QA刺激的PI周转。这些结果进一步支持了人脑新皮质中存在谷氨酸代谢型受体。此外，它们还表明在该脑区IP形成过程中，AMPA与谷氨酸代谢型受体激活之间存在浓度相关的双重相互作用。
