title: Guanosine may increase absence epileptic activity by means of A2A adenosine receptors in Wistar Albino Glaxo Rijswijk rats.
abstract: The non-adenosine nucleoside guanosine (Guo) was demonstrated to decrease quinolinic acid(QA)-induced seizures, spontaneously emerged absence epileptic seizures and lipopolysaccharide(LPS)-evoked induction of absence epileptic seizures suggesting its antiepileptic potential. It was also described previously that intraperitoneal (i.p.) injection of 20 and 50mg/kg Guo decreased the number of spike-wave discharges (SWDs) in a well investigated model of human absence epilepsy, the Wistar Albino Glaxo Rijswijk (WAG/Rij) rats during 4th (20mg/kg Guo) and 3rd as well as 4th (50mg/kg Guo) measuring hours. Guanosine can potentially decrease SWD number by means of its putative receptors but absence epileptic activity changing effects of Guo by means of increased extracellular adenosine (Ado) cannot be excluded. An increase in the dose of i.p. injected Guo is limited by its low solubility in saline, therefore, we addressed in the present study whether higher doses of Guo, diluted in sodium hydroxide (NaOH) solution, have more potent antiepileptic effect in WAG/Rij rats. We confirmed that i.p. 50mg/kg Guo decreased but, surprisingly, i.p. 100mg/kg Guo enhanced the number of SWDs in WAG/Rij rats. Combined i.p. injection of a non-selective Ado receptor antagonist theophylline (5mg/kg) or a selective Ado A2A receptor (A2AR) antagonist SCH 58261 (7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine) (1mg/kg) and a cyclooxygenase 1 and 2/COX-1 and COX-2 inhibitor indomethacin (10mg/kg) with 100mg/kg Guo decreased the SWD number compared to i.p. 100mg/kg Guo alone. The results suggest that i.p. 100mg/kg Guo can increase SWD number by means of the adenosinergic system.
authors.affiliation: Institute of Biology, University of Pécs, Pécs, Ifjúság útja 6., 7624, Hungary; Department of Zoology, University of West Hungary Savaria Campus, Szombathely, Károlyi Gáspár tér 4., 9700, Hungary. Electronic address: reni.lakatos@gmail.com.
authors.forename: Renáta Krisztina
authors.initials: RK
authors.lastname: Lakatos
authors.affiliation: MTA-ELTE NAP B Laboratory of Molecular and Systems Neurobiology, Institute of Biology, Hungarian Academy of Sciences and Eötvös Loránd University, Budapest, Pázmány Péter sétány 1C, 1117, Hungary; Laboratory of Neuromorphology and Human Brain Tissue Bank, Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, Tűzoltó u. 58., 1094, Hungary. Electronic address: dobolyi.arpad@med.semmelweis-univ.hu.
authors.forename: Árpád
authors.initials: Á
authors.lastname: Dobolyi
authors.affiliation: MTA-ELTE NAP B Laboratory of Molecular and Systems Neurobiology, Institute of Biology, Hungarian Academy of Sciences and Eötvös Loránd University, Budapest, Pázmány Péter sétány 1C, 1117, Hungary; Laboratory of Proteomics, Eötvös Loránd University, Budapest, Pázmány Péter sétány 1C, 1117, Hungary. Electronic address: mtodorov@t-online.hu.
authors.forename: Mihail Ivilinov
authors.initials: MI
authors.lastname: Todorov
authors.affiliation: Laboratory of Proteomics, Eötvös Loránd University, Budapest, Pázmány Péter sétány 1C, 1117, Hungary; Department of Physiology and Neurobiology, Eötvös Loránd University, Budapest, Pázmány Péter sétány 1C, 1117, Hungary. Electronic address: kakekesi@ttk.elte.hu.
authors.forename: Katalin A
authors.initials: KA
authors.lastname: Kékesi
authors.affiliation: Laboratory of Proteomics, Eötvös Loránd University, Budapest, Pázmány Péter sétány 1C, 1117, Hungary; MTA-TTK NAP MS Neuroproteomics Research Group, Hungarian Academy of Sciences, Budapest, Magyar tudósok körútja 2., 1117, Hungary. Electronic address: gjuhasz@dec001.geobio.elte.hu.
authors.forename: Gábor
authors.initials: G
authors.lastname: Juhász
authors.affiliation: Department of Botany, University of West Hungary Savaria Campus, Szombathely, Károlyi Gáspár tér 4., 9700, Hungary. Electronic address: aleksza.magdolna13@gmail.com.
authors.forename: Magdolna
authors.initials: M
authors.lastname: Aleksza
authors.affiliation: Department of Zoology, University of West Hungary Savaria Campus, Szombathely, Károlyi Gáspár tér 4., 9700, Hungary. Electronic address: zskovacs@ttk.nyme.hu.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Kovács
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000139:chemically induced*; D005583:Fourier Analysis; D006151:Guanosine / Q000009:adverse effects*; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D058915:Purinergic P1 Receptor Antagonists / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D013806:Theophylline / Q000494:pharmacology; D013997:Time Factors; D014230:Triazoles / Q000494:pharmacology
chemical_list: C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D058917:Adenosine A2 Receptor Antagonists; D000927:Anticonvulsants; D016861:Cyclooxygenase Inhibitors; D008070:Lipopolysaccharides; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; D014230:Triazoles; D006151:Guanosine; D013806:Theophylline; D007213:Indomethacin
keywords: Absence epilepsy; Adenosinergic system; Guanosine; WAG/Rij rats