Brammer M J, Richmond S, Xiang J Z, Adamson P, Hajimohammadreza I, Silva M A, Campbell I C
Department of Neuroscience, Institute of Psychiatry, London, U.K.
Neurosci Lett. 1991 Jul 22;128(2):231-4. doi: 10.1016/0304-3940(91)90267-w.
The effects of quisqualate and kainate on synaptosomal inositol phosphate (InsP) labelling, 45Ca influx and intrasynaptosomal free calcium ([Ca2+]i) were investigated. Each agonist caused a concentration-dependent increase in both [Ca2+]i and InsP labelling: quisqualate, however, produced significantly larger responses in both parameters and at lower EC50 values. Neither quisqualate or kainate significantly affected 45Ca influx into synaptosomes, indicating that the observed increases in [Ca2+]i were due to mobilisation from intracellular stores. The concentration-dependent increases in [Ca2+]i promoted by quisqualate and kainate were monophasic, whereas the increases in InsP formation fitted well to a biphasic curve. The EC50 values suggest that both kainate and quisqualate initially mobilise calcium from inositol 1,4,5-trisphosphate (Ins 1,4,5-P3)-sensitive stores and that the resultant increases in [Ca2+]i will, above a certain threshold, promote further increases in InsP production by stimulation of Ca(2+)-dependent phospholipase C. When saturating concentrations of kainate and quisqualate were used in combination, the effects on both InsP labelling and [Ca2+]i were not additive but were slightly higher than those produced by kainate alone: combined administration of the two agonists had no effect on 45Ca influx. These results suggest that kainate acts as a partial agonist at the presynaptic quisqualate metabotropic glutamatergic receptor.
研究了喹啉酸和海人酸对突触体肌醇磷酸（InsP）标记、45Ca内流和突触体内游离钙（[Ca2+]i）的影响。每种激动剂均引起[Ca2+]i和InsP标记呈浓度依赖性增加：然而，喹啉酸在这两个参数上均产生了明显更大的反应，且在较低的半数有效浓度（EC50）值时即出现。喹啉酸和海人酸均未显著影响45Ca流入突触体，这表明观察到的[Ca2+]i增加是由于细胞内钙库的释放。喹啉酸和海人酸促进的[Ca2+]i浓度依赖性增加是单相的，而InsP形成的增加则很好地拟合了双相曲线。EC50值表明，海人酸和喹啉酸最初均从对肌醇1,4,5-三磷酸（Ins 1,4,5-P3）敏感的钙库中释放钙，并且由此导致的[Ca2+]i增加在超过一定阈值时，将通过刺激钙依赖性磷脂酶C促进InsP生成的进一步增加。当使用饱和浓度的海人酸和喹啉酸联合使用时，对InsP标记和[Ca2+]i的影响并非相加性的，而是略高于单独使用海人酸时产生的影响：两种激动剂联合给药对45Ca内流无影响。这些结果表明，海人酸在突触前喹啉酸代谢型谷氨酸能受体上作为部分激动剂起作用。
