Kovács Z, Kékesi K A, Dobolyi Á, Lakatos R, Juhász G
Department of Zoology, University of West Hungary, Savaria Campus, Károlyi Gáspár tér 4., Szombathely 9700, Hungary.
Laboratory of Proteomics, Eötvös Loránd University, Pázmány Péter sétány 1C, Budapest 1117, Hungary; Department of Physiology and Neurobiology, Eötvös Loránd University, Pázmány Péter sétány 1C, Budapest 1117, Hungary.
Neuroscience. 2015 Aug 6;300:593-608. doi: 10.1016/j.neuroscience.2015.05.054. Epub 2015 May 30.
Adenosine (Ado) and non-adenosine (non-Ado) nucleosides such as inosine (Ino), guanosine (Guo) and uridine (Urd) may have regionally different roles in the regulation of physiological and pathophysiological processes in the central nervous system (CNS) such as epilepsy. It was demonstrated previously that Ino and Guo decreased quinolinic acid (QA)-induced seizures and Urd reduced penicillin-, bicuculline- and pentylenetetrazole (PTZ)-induced seizures. It has also been demonstrated that Ino and Urd may exert their effects through GABAergic system by altering the function of GABA(A) type of gamma-aminobutyric acid receptors (GABAA receptors) whereas Guo decreases glutamate-induced excitability through glutamatergic system, which systems (GABAergic and glutamatergic) are involved in pathomechanisms of absence epilepsy. Thus, we hypothesized that Ino and Guo, similarly to the previously described effect of Urd, might also decrease absence epileptic activity. We investigated in the present study whether intraperitoneal (i.p.) application of Ino (500 and 1000mg/kg), Guo (20 and 50mg/kg), Urd (500 and 1000mg/kg), GABA(A) receptor agonist muscimol (1 and 3mg/kg), GABA(A) receptor antagonist bicuculline (2 and 4mg/kg), non-selective Ado receptor antagonist theophylline (5 and 10mg/kg) and non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo (a,d) cyclohepten-5,10-imine maleate (MK-801, 0.0625 and 0.1250mg/kg) alone and in combination have modulatory effects on absence epileptic activity in Wistar Albino Glaxo Rijswijk (WAG/Rij) rats. We found that Guo decreased the number of spike-wave discharges (SWDs) whereas Ino increased it dose-dependently. We strengthened that Urd can decrease absence epileptic activity. Our results suggest that Guo, Urd and their analogs could be potentially effective drugs for treatment of human absence epilepsy.
腺苷（Ado）以及非腺苷（non-Ado）核苷，如肌苷（Ino）、鸟苷（Guo）和尿苷（Urd），在中枢神经系统（CNS）诸如癫痫等生理和病理生理过程的调节中可能具有区域差异作用。先前已证明，肌苷和鸟苷可减少喹啉酸（QA）诱导的癫痫发作，尿苷可减少青霉素、荷包牡丹碱和戊四氮（PTZ）诱导的癫痫发作。还已证明，肌苷和尿苷可能通过改变γ-氨基丁酸A型受体（GABAA受体）的功能，经γ-氨基丁酸能系统发挥作用，而鸟苷则通过谷氨酸能系统降低谷氨酸诱导的兴奋性，这两种系统（γ-氨基丁酸能和谷氨酸能）均参与失神癫痫的发病机制。因此，我们推测，与先前描述的尿苷作用类似，肌苷和鸟苷也可能减少失神癫痫活动。在本研究中，我们调查了腹腔注射（i.p.）肌苷（500和1000mg/kg）、鸟苷（20和50mg/kg）、尿苷（500和1000mg/kg）、GABAA受体激动剂蝇蕈醇（1和3mg/kg）、GABAA受体拮抗剂荷包牡丹碱（2和4mg/kg）、非选择性腺苷受体拮抗剂茶碱（5和10mg/kg）以及非竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂（+）-5-甲基-10,11-二氢-5H-二苯并（a,d）环庚烯-5,10-亚胺马来酸盐（MK-801，0.0625和0.1250mg/kg）单独及联合使用时，对Wistar白化大鼠（WAG/Rij）失神癫痫活动的调节作用。我们发现，鸟苷可减少棘波放电（SWD）的次数，而肌苷则剂量依赖性地增加其次数。我们进一步证实尿苷可减少失神癫痫活动。我们的结果表明，鸟苷、尿苷及其类似物可能是治疗人类失神癫痫的潜在有效药物。
