Lazarewicz J W, Wroblewski J T, Palmer M E, Costa E
Fidia-Georgetown Institute for the Neurosciences, Georgetown University School of Medicine, Washington, D.C. 20007.
Neuropharmacology. 1988 Jul;27(7):765-9. doi: 10.1016/0028-3908(88)90088-3.
In cultured granule cells prelabeled with [3H]arachidonate the activation of excitatory amino acid receptors by various agonists results in a dose-dependent stimulation of [3H]arachidonic acid release. Glutamate and aspartate were the most potent agonists, whereas N-methyl-D-aspartate, kainate and quisqualate were less potent. Other neurotransmitter receptor agonists--GABA, baclofen and norepinephrine--were inactive, while carbachol induced only a slight effect. Since the transmitter-mediated release of [3H]arachidonate was blocked by phencyclidine, a selective inhibitor of NMDA-sensitive glutamate receptors, it can be inferred that the effects of all other receptor agonists were indirectly mediated via the release of glutamate from granule cells. Aspartate-evoked release was Ca2+-dependent and was abolished by the glutamate receptor inhibitors: Mg2+ ions and 2-amino-5-phosphonovalerate. The inhibitors of phospholipase A2, quinacrine and p-bromophenacyl bromide, decreased the release of [3H]arachidonate in a dose-related manner.
在用[3H]花生四烯酸预标记的培养颗粒细胞中，各种激动剂对兴奋性氨基酸受体的激活会导致[3H]花生四烯酸释放呈剂量依赖性刺激。谷氨酸和天冬氨酸是最有效的激动剂，而N-甲基-D-天冬氨酸、海人酸和quisqualate的效力较低。其他神经递质受体激动剂——γ-氨基丁酸、巴氯芬和去甲肾上腺素——无活性，而卡巴胆碱仅产生轻微影响。由于[3H]花生四烯酸的递质介导释放被苯环利定（一种对NMDA敏感的谷氨酸受体的选择性抑制剂）阻断，因此可以推断所有其他受体激动剂的作用是通过颗粒细胞释放谷氨酸间接介导的。天冬氨酸诱发的释放依赖于Ca2+，并被谷氨酸受体抑制剂：Mg2+离子和2-氨基-5-磷酸戊酸所消除。磷脂酶A2抑制剂奎纳克林和对溴苯甲酰溴以剂量相关的方式降低了[3H]花生四烯酸的释放。
