NEUROPEPTIDES - A ROLE AS ENDOGENOUS MEDIATORS OR MODULATORS OF EPILEPTIC PHENOMENA
NEUROPEPTIDES - A ROLE AS ENDOGENOUS MEDIATORS OR MODULATORS OF EPILEPTIC PHENOMENA
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DOI：
10.1002/ana.410160707
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发表时间：
1984-01-01
影响因子：
11.2
通讯作者：
LOMAX, P
中科院分区：
文献类型：
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作者：
BAJOREK, JG;LEE, RJ;LOMAX, P
随着越来越多的中枢神经系统的小肽能成分被分离出来，它们在疾病状态中的作用正在研究中。这些神经肽中的一些，特别是阿片样肽、促肾上腺皮质激素和一些下丘脑释放因子，已被发现改变神经元的兴奋性。这一发现导致了这些肽可能在癫痫的发病机制中发挥作用的建议。我们在癫痫的遗传模型中测试了这一假设。在无毒剂量下，几种外源性肽具有抗惊厥特性，而其他肽则具有促惊厥作用。最有效的抗惊厥药是阿片样肽β-内啡肽。其作用类似于阿片类生物碱。使用强效拮抗剂盐酸纳洛酮来阻断可能的内源性阿片样肽，我们发现对未处理动物的癫痫发作无影响。然而，纳洛酮确实通过部分阻断进一步癫痫发作的发作后不应性来改变发作后事件。我们推测，内源性阿片肽的一个可能的作用可能是限制癫痫发作的蔓延或调节癫痫发作后对进一步癫痫发作的易感性。纳洛酮是有效的，在这个模型中，只有发生后的压力情况下，修改了癫痫发作，并推测诱导释放内源性阿片样肽。从其他癫痫模型支持这一假设进行了讨论。其他肽能系统也可能是活跃在各种癫痫模型，目前了解他们的作用进行审查。
As more small peptidergic components of the central nervous system are isolated, their role in disease states is being investigated. Several of these neuropeptides, especially the opioidlike peptides, adrenocorticotropic hormone, and some hypothalamic releasing factors, have been found to alter neuronal excitability. This finding has led to the proposal that these peptides may play a role in the pathogenesis of the epilepsies. We tested this hypothesis in a genetic model of epilepsy. At nontoxic doses, several exogenously administered peptides had anticonvulsant properties, while others were proconvulsant. The most potent anticonvulsant was the opioidlike peptide β‐endorphin. Its effect was similar to that of the opioid alkaloids. Using the potent antagonist naloxone hydrochloride to block possible endogenous opioid‐like peptides, we found no effects on seizures in naive animals. Naloxone did alter postictal events, however, by partially blocking the postictal refractoriness to further seizures. We speculate that one possible role for the endogenous opioid peptides may be to limit the spread of seizures or to modulate postictal susceptibility to further seizures. Naloxone was effective in this model only after stressful situations occurred that modified the seizures and presumably induced a release of endogenous opioidlike peptides. Support for this hypothesis from other epilepsy models is discussed. Other peptidergic systems may also be active in various epileptic models, and the current understanding of their roles is reviewed.