Schulte M K, Roon R J, Koerner J F
Department of Biochemistry, Medical School, University of Minnesota, Minneapolis 55455.
Brain Res. 1993 Mar 5;605(1):85-92. doi: 10.1016/0006-8993(93)91359-z.
Hippocampal CA1 pyramidal cell neurons are sensitized to depolarization by L-2-amino-4-phosphonobutanoic acid (L-AP4) following exposure to L-quisqualic acid (QUIS). It has been proposed that induction of this 'QUIS-effect' involves uptake of L-QUIS by hippocampal cells. We have used o-phthaldialdehyde (OPA) derivatization and high performance liquid chromatographic (HPLC) separation of extracts from hippocampal slices which have been exposed to varied concentrations of L-QUIS to investigate L-QUIS uptake into hippocampal slices. We observe uptake rates such that the internal concentration of L-QUIS exceeds the bath concentration within 7 min. The fact that this uptake is concentrative indicates that it is mediated by an active transport system. In addition, uptake of L-QUIS may be linked to the induction of the QUIS-effect. At low concentrations of L-QUIS (< 4 microM), the QUIS-effect is only partially induced within the 4 min incubation time which maximally induces the effect when 16 microM L-QUIS is used. However, repeated 4 min exposure periods of slices to low L-QUIS concentrations will eventually induce the QUIS-effect even when each exposure is separated by extensive washout periods. Hence induction is dependent on both concentration and total exposure time. We also examined the effects of L-alpha-aminoadipic acid and L-serine-O-sulfate on the rate of L-QUIS uptake. Exposure of slices to these compounds prior to treatment with L-QUIS will block the physiological effects of L-QUIS. We found that these 'pre-blocking' compounds did not decrease the rate of L-QUIS uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
海马体CA1锥体细胞神经元在暴露于L-使君子氨酸（QUIS）后，会对L-2-氨基-4-膦酰丁酸（L-AP4）的去极化作用敏感。有人提出，这种“QUIS效应”的诱导涉及海马体细胞对L-QUIS的摄取。我们使用邻苯二甲醛（OPA）衍生化和高效液相色谱（HPLC）分离法，对暴露于不同浓度L-QUIS的海马体切片提取物进行分析，以研究L-QUIS进入海马体切片的摄取情况。我们观察到摄取速率，使得L-QUIS的内部浓度在7分钟内超过浴槽浓度。这种摄取是浓缩性的，这一事实表明它是由一个主动转运系统介导的。此外，L-QUIS的摄取可能与QUIS效应的诱导有关。在低浓度L-QUIS（<4 microM）时，在4分钟的孵育时间内，QUIS效应仅部分被诱导，而当使用16 microM L-QUIS时，该效应能最大程度地被诱导。然而，即使每次暴露之间有大量的洗脱期，将切片反复暴露于低L-QUIS浓度下4分钟，最终也会诱导出QUIS效应。因此，诱导既取决于浓度，也取决于总暴露时间。我们还研究了L-α-氨基己二酸和L-丝氨酸-O-硫酸盐对L-QUIS摄取速率的影响。在用L-QUIS处理之前，将切片暴露于这些化合物中会阻断L-QUIS的生理效应。我们发现这些“预阻断”化合物并没有降低L-QUIS的摄取速率。（摘要截断于250字）
