Conner-Kerr T A, Terrian D M
Department of Anatomy and Cell Biology, East Carolina University School of Medicine, Greenville, NC 27858.
Brain Res Bull. 1993;31(5):573-80. doi: 10.1016/0361-9230(93)90125-u.
U-54494A, a 1,2-diamine, is a potent inhibitor of glutamate release in a synaptosomal preparation that is highly enriched with hippocampal mossy fiber (MF) nerve endings. At a concentration of 100 microM, U-54494A significantly reduced the availability of cytosolic free calcium (Ca2+) in depolarized MF-enriched synaptosomes by 30% and inhibited the K(+)-evoked release of endogenous glutamate by 85%. The extent to which glutamate release was inhibited allows us to conclude that U-54494A acts directly on the MF subpopulation of glutamatergic nerve endings in the guinea pig hippocampus. In addition, this anticonvulsant effectively countered the presynaptic facilitation of K(+)-evoked glutamate release that is induced by kainic acid (KA). Thus, while KA (1 mM) by itself nearly doubled the rate of K(+)-evoked glutamate release, there was no net increase in the presence of both KA and U-54494A (100 microM). However, the opposed effects of these two compounds on glutamate release do not appear to be due to a direct interaction. In the presence of U-54494A (100 microM), KA (1 mM) significantly enhanced the K(+)-evoked release of glutamate. Finally, it is demonstrated that the KA-induced enhancement of glutamate release does not require the depolarization-induced entry of extracellular Ca2+.
U - 54494A，一种1,2 - 二胺，是突触体准备中谷氨酸释放的强效抑制剂，该突触体高度富集海马苔藓纤维（MF）神经末梢。在100微摩尔浓度下，U - 54494A使去极化的富含MF的突触体中胞质游离钙（Ca2 +）的可利用性显著降低30%，并抑制钾离子（K(+)）诱发的内源性谷氨酸释放85%。谷氨酸释放被抑制的程度使我们得出结论，U - 54494A直接作用于豚鼠海马中谷氨酸能神经末梢的MF亚群。此外，这种抗惊厥药有效对抗了由红藻氨酸（KA）诱导的K(+)诱发的谷氨酸释放的突触前易化作用。因此，虽然单独使用KA（1毫摩尔）几乎使K(+)诱发的谷氨酸释放速率增加一倍，但在KA和U - 54494A（100微摩尔）同时存在时并没有净增加。然而，这两种化合物对谷氨酸释放的相反作用似乎不是由于直接相互作用。在U - 54494A（100微摩尔）存在的情况下，KA（1毫摩尔）显著增强了K(+)诱发的谷氨酸释放。最后，证明了KA诱导的谷氨酸释放增强并不需要去极化诱导的细胞外Ca2 +内流。
