title: Investigation into effects of antipsychotics on ectonucleotidase and adenosine deaminase in zebrafish brain.
abstract: Antipsychotic agents are used for the treatment of psychotic symptoms in patients with several brain disorders, such as schizophrenia. Atypical and typical antipsychotics differ regarding their clinical and side-effects profile. Haloperidol is a representative typical antipsychotic drug and has potent dopamine receptor antagonistic functions; however, atypical antipsychotics have been developed and characterized an important advance in the treatment of schizophrenia and other psychotic disorders. Purine nucleotides and nucleosides, such as ATP and adenosine, constitute a ubiquitous class of extracellular signaling molecules crucial for normal functioning of the nervous system. Indirect findings suggest that changes in the purinergic system, more specifically in adenosinergic activity, could be involved in the pathophysiology of schizophrenia. We investigated the effects of typical and atypical antipsychotics on ectonucleotidase and adenosine deaminase (ADA) activities, followed by an analysis of gene expression patterns in zebrafish brain. Haloperidol treatment (9 µM) was able to decrease ATP hydrolysis (35%), whereas there were no changes in hydrolysis of ADP and AMP in brain membranes after antipsychotic exposure. Adenosine deamination in membrane fractions was inhibited (38%) after haloperidol treatment when compared to the control; however, no changes were observed in ADA soluble fractions after haloperidol exposure. Sulpiride (250 µM) and olanzapine (100 µM) did not alter ectonucleotidase and ADA activities. Haloperidol also led to a decrease in entpd2_mq, entpd3 and adal mRNA transcripts. These findings demonstrate that haloperidol is an inhibitor of NTPDase and ADA activities in zebrafish brain, suggesting that purinergic signaling may also be a target of pharmacological effects promoted by this drug.
authors.affiliation: 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, Avenida Ipiranga, 6681, Porto Alegre, RS, 90619-900, Brazil.
authors.forename: Kelly Juliana
authors.initials: KJ
authors.lastname: Seibt
authors.affiliation: 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, Avenida Ipiranga, 6681, Porto Alegre, RS, 90619-900, Brazil.
authors.forename: Renata da Luz
authors.initials: Rda L
authors.lastname: Oliveira
authors.affiliation: Laboratório de Biologia Genômica e Molecular, 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, Avenida Ipiranga, 6681, Porto Alegre, RS, 90619-900, Brazil.
authors.forename: Mauricio Reis
authors.initials: MR
authors.lastname: Bogo
authors.affiliation: Laboratório de Bioquímica Experimental e Computacional de Fármacos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Avenida Brasil, 4365, Rio de Janeiro, RJ, 21040-360, Brazil. mario.senger@ioc.fiocruz.br.
authors.forename: Mario Roberto
authors.initials: MR
authors.lastname: Senger
authors.affiliation: 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, Avenida Ipiranga, 6681, Porto Alegre, RS, 90619-900, Brazil. cbonan@pucrs.br.
authors.forename: Carla Denise
authors.initials: CD
authors.lastname: Bonan
mesh_terms: D000243:Adenosine Deaminase / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000201:enzymology*; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D006868:Hydrolysis; D008297:Male; D000077152:Olanzapine; D013469:Sulpiride / Q000494:pharmacology; D015027:Zebrafish / Q000502:physiology*; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D029961:Zebrafish Proteins; D001569:Benzodiazepines; D013469:Sulpiride; D000243:Adenosine Deaminase; D000251:Adenosine Triphosphatases; C027201:ectoATPase; D006220:Haloperidol; D000077152:Olanzapine
keywords: Adenosine deaminase; Antipsychotic; Ectonucleotidases; Haloperidol; Zebrafish