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Investigation into effects of antipsychotics on ectonucleotidase and adenosine deaminase in zebrafish brain

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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.

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Acknowledgments

This work was supported by DECIT/SCTIEMS through Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS, Proc. 10/0036-5, conv. 700545/2008). K.J.S. was a recipient of a fellowship from Programa PROBOLSAS/PUCRS. R.L.O. was a recipient of a fellowship from PIBIC/CNPq/PUCRS. M.R.S. was a recipient of a fellowship from CNPq. The authors also would like to thank Cladinara Sarturi for technical assistance.

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  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, Avenida Ipiranga, 6681, Porto Alegre, RS, 90619-900, Brazil

    Kelly Juliana Seibt, Renata da Luz Oliveira & Carla Denise Bonan

  2. 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

    Mauricio Reis Bogo

  3. 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 Roberto Senger

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  1. Kelly Juliana Seibt
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Correspondence to Mario Roberto Senger or Carla Denise Bonan.

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Seibt, K.J., da Luz Oliveira, R., Bogo, M.R. et al. Investigation into effects of antipsychotics on ectonucleotidase and adenosine deaminase in zebrafish brain. Fish Physiol Biochem 41, 1383–1392 (2015). https://doi.org/10.1007/s10695-015-0093-2

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