Magnuson D S, Curry K, Peet M J, McLennan H
Department of Physiology, University of British Columbia, Vancouver, Canada.
Exp Brain Res. 1988;73(3):541-5. doi: 10.1007/BF00406612.
The conformational requirements for activation of N-methyl-D-aspartate (NMDA) and quisqualate (QUIS) excitatory amino acid receptors on rat spinal neurones in vitro have been examined using a number of conformationally restricted compounds related to L-glutamate (L-GLU). The excitants were assigned to a receptor type on the basis of their susceptibility to blockade by D (-)-2-amino-5-phosphonvalerate (DAPV) and kynurenate (KYNA). When iontophoretically applied to unidentified neurones in the dorsal horn of spinal cord slices maintained in vitro, three of the isomers of 1-amino-1,3-cyclopentane dicarboxylate (ACPD) evoked excitations which were DAPV-sensitive and therefore were probably elicited via NMDA receptors. The fourth isomer (D-trans-(1R,3S)-ACPD) resembled quinolinate (QUIN) in its actions, and differed from both NMDA and QUIS. Several pyridine derivatives in addition to QUIN were tested, and both the 2,5- and 2,6-pyridine dicarboxylates evoked excitations which, like those produced by QUIS and L-GLU, were largely unaffected by both DAPV and KYNA and thus appeared due to activation of the QUIS receptor. 2,4-Pyridine dicarboxylate acted as a weak and unselective antagonist of amino acid-induced excitations. The results support an earlier conclusion that compounds reacting with the NMDA receptor do so in an extended configuration whereas the QUIS receptor has a more folded template. The possibility that QUIN reacts with a receptor different from those activated by other amino acids is considered.
利用一系列与L-谷氨酸（L-GLU）相关的构象受限化合物，研究了体外培养的大鼠脊髓神经元上N-甲基-D-天冬氨酸（NMDA）和喹啉酸（QUIS）兴奋性氨基酸受体激活的构象要求。根据它们对D-（-）-2-氨基-5-磷酸戊酸（DAPV）和犬尿烯酸（KYNA）阻断的敏感性，将这些兴奋剂归为一种受体类型。当通过离子电泳法应用于体外培养的脊髓切片背角中未鉴定的神经元时，1-氨基-1,3-环戊烷二羧酸（ACPD）的三种异构体引起了兴奋，这些兴奋对DAPV敏感，因此可能是通过NMDA受体引发的。第四种异构体（D-反式-（1R,3S）-ACPD）的作用类似于喹啉酸（QUIN），与NMDA和QUIS均不同。除了QUIN之外，还测试了几种吡啶衍生物，2,5-吡啶二羧酸和2,6-吡啶二羧酸均引起了兴奋，与QUIS和L-GLU产生的兴奋一样，它们在很大程度上不受DAPV和KYNA的影响，因此似乎是由于QUIS受体的激活所致。2,4-吡啶二羧酸作为氨基酸诱导兴奋的弱效且非选择性拮抗剂。结果支持了一个早期结论，即与NMDA受体反应的化合物以伸展构型进行反应，而QUIS受体具有更折叠的模板。文中考虑了QUIN与不同于其他氨基酸激活的受体反应的可能性。
