title: Role of adenosine signaling on pentylenetetrazole-induced seizures in zebrafish.
abstract: Adenosine is a well-known endogenous modulator of neuronal excitability with anticonvulsant properties. Thus, the modulation exerted by adenosine might be an effective tool to control seizures. In this study, we investigated the effects of drugs that are able to modulate adenosinergic signaling on pentylenetetrazole (PTZ)-induced seizures in adult zebrafish. The adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) decreased the latency to the onset of the tonic-clonic seizure stage. The adenosine A1 receptor agonist cyclopentyladenosine (CPA) increased the latency to reach the tonic-clonic seizure stage. Both the adenosine A2A receptor agonist and antagonist, CGS 21680 and ZM 241385, respectively, did not promote changes in seizure parameters. Pretreatment with the ecto-5'nucleotidase inhibitor adenosine 5'-(α,β-methylene) diphosphate (AMPCP) decreased the latency to the onset of the tonic-clonic seizure stage. However, when pretreated with the adenosine deaminase (ADA) inhibitor, erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA), or with the nucleoside transporter (NT) inhibitors, dipyridamole and S-(4-Nitrobenzyl)-6-thioinosine (NBTI), animals showed longer latency to reach the tonic-clonic seizure status. Finally, our molecular analysis of the c-fos gene expression corroborates these behavioral results. Our findings indicate that the activation of adenosine A1 receptors is an important mechanism to control the development of seizures in zebrafish. Furthermore, the actions of ecto-5'-nucleotidase, ADA, and NTs are directly involved in the control of extracellular adenosine levels and have an important role in the development of seizure episodes in zebrafish.
authors.affiliation: 1 Laboratório de Neuroquímica e Psicofarmacologia, Departamento de Biologia Celular e Molecular, Programa de Pós-Graduação em Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul , Porto Alegre, Brazil .
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Siebel
authors.forename: Fabiano Peres
authors.initials: FP
authors.lastname: Menezes
authors.forename: Katiucia Marques
authors.initials: KM
authors.lastname: Capiotti
authors.forename: Luiza Wilges
authors.initials: LW
authors.lastname: Kist
authors.forename: Isabel
authors.initials: I
authors.lastname: da Costa Schaefer
authors.forename: Juliana Zanetti
authors.initials: JZ
authors.lastname: Frantz
authors.forename: Maurício Reis
authors.initials: MR
authors.lastname: Bogo
authors.forename: Rosane Souza
authors.initials: RS
authors.lastname: Da Silva
authors.forename: Carla Denise
authors.initials: CD
authors.lastname: Bonan
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001593:Benzyl Compounds / Q000494:pharmacology; D003292:Convulsants / Q000633:toxicity; D004176:Dipyridamole / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos / Q000235:genetics / Q000502:physiology; D010433:Pentylenetetrazole / Q000633:toxicity*; D010627:Phenethylamines / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013868:Thioinosine / Q000031:analogs & derivatives / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology; D015027:Zebrafish
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D001593:Benzyl Compounds; D003292:Convulsants; D010627:Phenethylamines; D010726:Phosphodiesterase Inhibitors; D014970:Xanthines; C509055:erythro-(3-nonyl-p-aminobenzyl-adenine); C523965:alpha,beta-methyleneadenosine 5'-diphosphate; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D013868:Thioinosine; D000244:Adenosine Diphosphate; D004176:Dipyridamole; C051360:1,3-dipropyl-8-cyclopentylxanthine; C001789:4-nitrobenzylthioinosine; D000225:Adenine; D000241:Adenosine; D010433:Pentylenetetrazole