McCaslin P P, Morgan W W
University of Texas Health Science Center, Department of Cellular and Structural Biology, San Antonio, TX 78284-7762.
Brain Res. 1987 Aug 11;417(2):380-4. doi: 10.1016/0006-8993(87)90469-0.
Primary cultures of neurons from 8-day-old rat pups were grown for 10 days in vitro in antibiotic-free media and then analysed for changes in cyclic guanosine monophosphate (cGMP) in response to several excitatory amino acid (EAA) agonists or related antagonists. Kainic acid (KA), N-methyl-D-aspartic acid (NMDA) and quisqualic acid (QA) produced dose- and calcium-dependent increases in cGMP with KA producing the largest and QA the least increase in this cyclic nucleotide. The increase induced by NMDA was additive with both KA and QA; however, KA and QA were not additive with each other. In fact, QA completely antagonized the effects of KA and to a much greater degree than did the EAA antagonists, glutamylaminomethylsulfonic acid (GAMS) or cis-2,3-piperidine dicarboxylic acid (PDA). 2-Amino-7-phosphonoheptanoic acid completely prevented the NMDA-induced elevations of cGMP yet had little effect on either the KA- or QA-induced elevations of this parameter. GAMS and PDA, on the other hand, were more effective in blocking the effects of KA and QA than of NMDA. These data show that cGMP levels in cerebellar granule cells provide an excellent model for studying the subtypes of EAA receptors.
将8日龄大鼠幼崽的神经元原代培养物在无抗生素培养基中体外培养10天，然后分析其环磷酸鸟苷（cGMP）对几种兴奋性氨基酸（EAA）激动剂或相关拮抗剂的反应变化。海人酸（KA）、N-甲基-D-天冬氨酸（NMDA）和喹啉酸（QA）可使cGMP产生剂量和钙依赖性增加，其中KA引起的这种环核苷酸增加最大，QA最小。NMDA诱导的增加与KA和QA均呈相加作用；然而，KA和QA之间不存在相加作用。事实上，QA完全拮抗KA的作用，且比EAA拮抗剂谷氨酰胺甲基磺酸（GAMS）或顺式-2,3-哌啶二羧酸（PDA）的拮抗作用程度大得多。2-氨基-7-磷酸庚酸完全阻止了NMDA诱导的cGMP升高，但对KA或QA诱导的该参数升高影响很小。另一方面，GAMS和PDA在阻断KA和QA的作用方面比阻断NMDA更有效。这些数据表明，小脑颗粒细胞中的cGMP水平为研究EAA受体亚型提供了一个极佳的模型。
