Guanosine may increase absence epileptic activity by means of A2A adenosine receptors in Wistar Albino Glaxo Rijswijk rats

Renáta Krisztina Lakatos, A. Dobolyi, Mihail Ivilinov Todorov, K. Kékesi, G. Juhász, M. Aleksza, Z. Kovács

Research output: Article

7 Citations (Scopus)

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 50 mg/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 (20 mg/kg Guo) and 3rd as well as 4th (50 mg/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. 50 mg/kg Guo decreased but, surprisingly, i.p. 100 mg/kg Guo enhanced the number of SWDs in WAG/Rij rats. Combined i.p. injection of a non-selective Ado receptor antagonist theophylline (5 mg/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) (1 mg/kg) and a cyclooxygenase 1 and 2/COX-1 and COX-2 inhibitor indomethacin (10 mg/kg) with 100 mg/kg Guo decreased the SWD number compared to i.p. 100 mg/kg Guo alone. The results suggest that i.p. 100 mg/kg Guo can increase SWD number by means of the adenosinergic system.

Original languageEnglish
Pages (from-to)172-181
Number of pages10
JournalBrain Research Bulletin
Volume124
DOIs
Publication statusPublished - jún. 1 2016

Fingerprint

Adenosine A2A Receptors
Guanosine
Absence Epilepsy
Intraperitoneal Injections
Anticonvulsants
Epilepsy
Adenosine A2 Receptor Antagonists
Purinergic P1 Receptor Antagonists
Quinolinic Acid
Sodium Hydroxide
Cyclooxygenase 1
Cyclooxygenase 2 Inhibitors
Cyclooxygenase 2
Theophylline
Nucleosides
Indomethacin
Adenosine
Solubility

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

@article{a41aafd749fb4c5a9202686a9a6be2e1,
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 50 mg/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 (20 mg/kg Guo) and 3rd as well as 4th (50 mg/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. 50 mg/kg Guo decreased but, surprisingly, i.p. 100 mg/kg Guo enhanced the number of SWDs in WAG/Rij rats. Combined i.p. injection of a non-selective Ado receptor antagonist theophylline (5 mg/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) (1 mg/kg) and a cyclooxygenase 1 and 2/COX-1 and COX-2 inhibitor indomethacin (10 mg/kg) with 100 mg/kg Guo decreased the SWD number compared to i.p. 100 mg/kg Guo alone. The results suggest that i.p. 100 mg/kg Guo can increase SWD number by means of the adenosinergic system.",
keywords = "Absence epilepsy, Adenosinergic system, Guanosine, WAG/Rij rats",
author = "Lakatos, {Ren{\'a}ta Krisztina} and A. Dobolyi and Todorov, {Mihail Ivilinov} and K. K{\'e}kesi and G. Juh{\'a}sz and M. Aleksza and Z. Kov{\'a}cs",
year = "2016",
month = "6",
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language = "English",
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pages = "172--181",
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issn = "0361-9230",
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TY - JOUR

T1 - Guanosine may increase absence epileptic activity by means of A2A adenosine receptors in Wistar Albino Glaxo Rijswijk rats

AU - Lakatos, Renáta Krisztina

AU - Dobolyi, A.

AU - Todorov, Mihail Ivilinov

AU - Kékesi, K.

AU - Juhász, G.

AU - Aleksza, M.

AU - Kovács, Z.

PY - 2016/6/1

Y1 - 2016/6/1

N2 - 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 50 mg/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 (20 mg/kg Guo) and 3rd as well as 4th (50 mg/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. 50 mg/kg Guo decreased but, surprisingly, i.p. 100 mg/kg Guo enhanced the number of SWDs in WAG/Rij rats. Combined i.p. injection of a non-selective Ado receptor antagonist theophylline (5 mg/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) (1 mg/kg) and a cyclooxygenase 1 and 2/COX-1 and COX-2 inhibitor indomethacin (10 mg/kg) with 100 mg/kg Guo decreased the SWD number compared to i.p. 100 mg/kg Guo alone. The results suggest that i.p. 100 mg/kg Guo can increase SWD number by means of the adenosinergic system.

AB - 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 50 mg/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 (20 mg/kg Guo) and 3rd as well as 4th (50 mg/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. 50 mg/kg Guo decreased but, surprisingly, i.p. 100 mg/kg Guo enhanced the number of SWDs in WAG/Rij rats. Combined i.p. injection of a non-selective Ado receptor antagonist theophylline (5 mg/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) (1 mg/kg) and a cyclooxygenase 1 and 2/COX-1 and COX-2 inhibitor indomethacin (10 mg/kg) with 100 mg/kg Guo decreased the SWD number compared to i.p. 100 mg/kg Guo alone. The results suggest that i.p. 100 mg/kg Guo can increase SWD number by means of the adenosinergic system.

KW - Absence epilepsy

KW - Adenosinergic system

KW - Guanosine

KW - WAG/Rij rats

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