title: Absence epileptic activity changing effects of non-adenosine nucleoside inosine, guanosine and uridine in Wistar Albino Glaxo Rijswijk rats.
abstract: 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.
authors.affiliation: Department of Zoology, University of West Hungary, Savaria Campus, Károlyi Gáspár tér 4., Szombathely 9700, Hungary. Electronic address: zskovacs@ttk.nyme.hu.
authors.forename: Z
authors.initials: Z
authors.lastname: Kovács
authors.affiliation: 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. Electronic address: kakekesi@dec001.geobio.elte.hu.
authors.forename: K A
authors.initials: KA
authors.lastname: Kékesi
authors.affiliation: MTA-ELTE NAP Laboratory of Molecular and Systems Neurobiology, Institute of Biology, Hungarian Academy of Sciences and Eötvös Loránd University, Pázmány Péter sétány 1C, Budapest 1117, Hungary; Laboratory of Neuromorphology and Human Brain Tissue Bank, Department of Anatomy, Histology and Embryology, Semmelweis University, Tűzoltó u. 58., Budapest 1094, Hungary. Electronic address: dobolyi.arpad@med.semmelweis-univ.hu.
authors.forename: Á
authors.initials: Á
authors.lastname: Dobolyi
authors.affiliation: Department of Zoology, University of West Hungary, Savaria Campus, Károlyi Gáspár tér 4., Szombathely 9700, Hungary. Electronic address: reni.lakatos@gmail.com.
authors.forename: R
authors.initials: R
authors.lastname: Lakatos
authors.affiliation: Laboratory of Proteomics, Eötvös Loránd University, Pázmány Péter sétány 1C, Budapest 1117, Hungary; MTA-TTK NAP MS Neuroproteomics Research Group, Hungarian Academy of Sciences, Magyar tudósok körútja 2., Budapest 1117, Hungary. Electronic address: gjuhasz@dec001.geobio.elte.hu.
authors.forename: G
authors.initials: G
authors.lastname: Juhász
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000069280:Electrocorticography; D004832:Epilepsy, Absence / Q000188:drug therapy* / Q000503:physiopathology; D006151:Guanosine / Q000494:pharmacology*; D007288:Inosine / Q000494:pharmacology*; D008297:Male; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D014529:Uridine / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D018047:Receptors, Purinergic P1; D006151:Guanosine; D007288:Inosine; D014529:Uridine
keywords: WAG/Rij rats; absence epilepsy; guanosine; inosine; uridine