EFFECT OF PROPENTOFYLLINE (HWA-285) ON EXTRACELLULAR PURINES AND EXCITATORY AMINO-ACIDS IN CA1 OF RAT HIPPOCAMPUS DURING TRANSIENT ISCHEMIA
EFFECT OF PROPENTOFYLLINE (HWA-285) ON EXTRACELLULAR PURINES AND EXCITATORY AMINO-ACIDS IN CA1 OF RAT HIPPOCAMPUS DURING TRANSIENT ISCHEMIA
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DOI：
10.1111/j.1476-5381.1990.tb14097.x
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发表时间：
1990-08-01
影响因子：
7.3
通讯作者：
HAGBERG, H
中科院分区：
文献类型：
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作者：
ANDINE, P;RUDOLPHI, KA;HAGBERG, H
1腺苷摄取阻滞剂Proentofylline(HWA285)先前已被证明可以保护海马CA1区锥体细胞免受缺血诱导的迟发性神经元死亡。观察了丙戊茶碱对短暂性前脑缺血大鼠海马区CA1区细胞外嘌呤、天冬氨酸和谷氨酸浓度的影响。2采用四血管结扎法造成Wistar大鼠脑缺血20min，用微透析法采集细胞外化合物，用固定在透析器上的钨电极记录脑电。3丙戊茶碱(10 mg·kg~(-1)ip)不影响海马体透析液中任何化合物的基础水平。4诱导大鼠脑缺血后20 S内脑电转为等电。5细胞外腺苷、肌苷、次黄嘌呤、天冬氨酸和谷氨酸在缺血时升高数倍，在复流早期保持升高。再灌流后2小时内，所有化合物的浓度均恢复正常。6丙戊茶碱(10 mg·kg~(-1)I.P.)缺血前15分钟给药显着增加缺血引起的腺苷升高，但抑制其他嘌呤分解代谢产物和谷氨酸的增加。7单独进行体外实验，丙戊茶碱不抑制腺苷脱氨酶活性。8目前的资料表明，在体缺血时，丙戊茶碱可提高细胞外腺苷水平，降低细胞外谷氨酸水平。这些发现可能与丙戊茶碱的神经保护特性有关。
1 The adenosine uptake blocker propentofylline (HWA 285) has previously been shown to protect hippocampal CA1 pyramidal cells from ischaemia-induced delayed neuronal death. The influence of propentofylline, on the extracellular concentrations of purines, aspartate and glutamate in the CA1 of the rat hippocampus during transient forebrain ischaemia was investigated. 2 Twenty min of ischaemia was induced by four-vessel occlusion in Wistar rats, extracellular compounds were sampled by use of microdialysis and EEG was recorded by a tungsten electrode attached to the dialysis probe. 3 Propentofylline (10 mg kg-1 i.p.) did not influence the basal levels of any of the compounds in the hippocampal dialysates. 4 The EEG became isoelectric within 20 s after induction of ischaemia. 5 Extracellular adenosine, inosine, hypoxanthine, aspartate and glutamate increased several fold during ischaemia and remained elevated during early reflow. Within 2 h of reperfusion the concentration of all compounds was normalized. Xanthine increased upon reperfusion and remained elevated after 2 h. 6 Propentofylline (10 mg kg-1 i.p.) administered 15 min before ischaemia significantly enhanced the ischaemia-evoked increase of adenosine but attenuated the increases of the other purine catabolites and of glutamate. 7 The separate in vitro experiments, propentofylline did not inhibit adenosine deaminase activity. 8 The present data show that propentofylline enhances extracellular adenosine and lowers extracellular glutamate in vivo during ischaemia. These findings may be important in relation to the neuroprotective properties of propentofylline.