PUBLICATION
Role of Adenosine Signaling on Pentylenetetrazole-Induced Seizures in Zebrafish
- Authors
- Siebel, A.M., Menezes, F.P., Capiotti, K.M., Kist, L.W., Schaefer, I.D., Frantz, J.Z., Bogo, M.R., Da Silva, R.S., Bonan, C.D.
- ID
- ZDB-PUB-150107-5
- Date
- 2015
- Source
- Zebrafish 12(2): 127-36 (Journal)
- Registered Authors
- Bonan, Carla Denise
- Keywords
- none
- MeSH Terms
-
- Adenine/analogs & derivatives
- Adenine/pharmacology
- Adenosine/analogs & derivatives
- Adenosine/metabolism*
- Adenosine/pharmacology
- Adenosine A1 Receptor Antagonists/pharmacology
- Adenosine Diphosphate/analogs & derivatives
- Adenosine Diphosphate/pharmacology
- Animals
- Benzyl Compounds/pharmacology
- Convulsants/toxicity
- Dipyridamole/pharmacology
- Gene Expression Regulation/drug effects
- Genes, fos/genetics
- Genes, fos/physiology
- Pentylenetetrazole/toxicity*
- Phenethylamines/pharmacology
- Phosphodiesterase Inhibitors/pharmacology
- Seizures/chemically induced*
- Seizures/metabolism
- Signal Transduction/drug effects*
- Thioinosine/analogs & derivatives
- Thioinosine/pharmacology
- Xanthines/pharmacology
- Zebrafish*
- PubMed
- 25560904 Full text @ Zebrafish
Citation
Siebel, A.M., Menezes, F.P., Capiotti, K.M., Kist, L.W., Schaefer, I.D., Frantz, J.Z., Bogo, M.R., Da Silva, R.S., Bonan, C.D. (2015) Role of Adenosine Signaling on Pentylenetetrazole-Induced Seizures in Zebrafish. Zebrafish. 12(2):127-36.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping