NMDA受体激活对人大脑皮质中quisqualate刺激的磷脂酰肌醇周转的抑制作用。

Inhibitory effect of NMDA receptor activation on quisqualate-stimulated phosphatidylinositol turnover in the human cerebral cortex.

作者信息

Morari M, Calo G, Antonelli T, Gaist G, Acciarri N, Fabrizi A, Bianchi C, Beani L

机构信息

Institute of Pharmacology, University of Ferrara, Italy.

出版信息

Brain Res. 1991 Jul 5;553(1):14-7. doi: 10.1016/0006-8993(91)90223-i.

DOI:10.1016/0006-8993(91)90223-i

PMID:1834301

Abstract

The effect of excitatory amino acids (EAA) on the phosphatidylinositol (PI) turnover in human cerebral cortical slices was investigated. Quisqualic acid (QA) and, to lesser extent, ibotenic acid (IBO) at 10(-5)-10(-3) M increased inositol phosphate (IP) accumulation. L-Glutamic acid (L-glu), kainic acid (KA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartic acid (NMDA) were ineffective. NMDA dose-dependently antagonized the QA facilitatory effect. Such inhibition was prevented by the NMDA receptor complex antagonists (+)-5-methyl-10,11-dihydro-5H-dibenzo[a, d]cyclohepten-5,10-imine (MK-801) and by 3[+/-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid. The effect of IBO (but not that of QA) was greatly potentiated by MK-801. These data suggest that the EAA metabotropic receptor described in the rodent brain is also present in human cerebral cortex and is negatively modulated by the NMDA receptor.

摘要

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。在10（-5）-10（-3）M浓度下，quisqualic酸（QA）以及在较小程度上的鹅膏蕈氨酸（IBO）可增加肌醇磷酸（IP）的积累。L-谷氨酸（L-glu）、 kainic酸（KA）、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸和N-甲基-D-天冬氨酸（NMDA）无效。NMDA剂量依赖性地拮抗QA的促进作用。NMDA受体复合物拮抗剂（+）-5-甲基-10,11-二氢-5H-二苯并[a,d]环庚烯-5,10-亚胺（MK-801）和3[（+/-）-2-羧基哌嗪-4-基]丙基-1-膦酸可防止这种抑制作用。MK-801可大大增强IBO（而非QA）的作用。这些数据表明，啮齿动物脑中描述的EAA促代谢型受体也存在于人脑皮质中，并受到NMDA受体的负调节。