Foster A C, Mena E E, Monaghan D T, Cotman C W
Nature. 1981 Jan 1;289(5793):73-5. doi: 10.1038/289073a0.
The heterocyclic compound kainic acid (KA) is a potent excitant when applied to mammalian neurones. Lesions caused by injections of KA into the rat striatum and hippocampus cause similar patterns of damage to those seen in Huntington's chorea and status epilepticus, respectively. Although it was originally thought to be a glutamate agonist, it is now clear that KA does not act on the majority of the receptors for glutamate, and in fact seems to act on a class of receptors which are distinct from those which mediate responses to other excitatory amino acids. The potent and selective neurotoxic effects of this compound may be mediated by these same receptors. At present, the relative distribution of junctional and extrajunctional (non-synaptic) receptors is unknown and resolution of this issue would provide important insights into the action of KA on the central nervous system (CNS). We show here that KA binding sites are greatly enriched in isolated synaptic junctions from rat brain and, using an in vitro autoradiographic technique, we have found that these binding sites are concentrated specifically in terminal fields where KA acts as a potent neurotoxin.
杂环化合物海藻酸(KA)作用于哺乳动物神经元时是一种强效兴奋剂。向大鼠纹状体和海马体注射KA所造成的损伤,分别与亨廷顿舞蹈症和癫痫持续状态中的损伤模式相似。尽管最初认为它是一种谷氨酸激动剂,但现在很清楚KA并不作用于大多数谷氨酸受体,实际上它似乎作用于一类与介导对其他兴奋性氨基酸反应的受体不同的受体。这种化合物强大的选择性神经毒性作用可能由这些相同的受体介导。目前,突触结合部和突触外(非突触)受体的相对分布尚不清楚,解决这个问题将为KA对中枢神经系统(CNS)的作用提供重要见解。我们在此表明,KA结合位点在从大鼠脑分离出的突触结合部中大量富集,并且使用体外放射自显影技术,我们发现这些结合位点特别集中在KA作为强效神经毒素起作用的终末区域。