Antipsychotic drugs inhibit nucleotide hydrolysis in zebrafish (Danio rerio) brain membranes

Seibt, Kelly Juliana; Oliveira, Renata da Luz; Rico, Eduardo Pacheco; Dias, Renato Dutra; Bogo, Maurı́cio Reis; Bonan, Carla Denise

doi:10.1016/j.tiv.2008.10.003

Cited by 24 publications

(17 citation statements)

References 38 publications

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“…The expression of AChE was decreased on 1st day, after 7 days exposure, it was up-regulated significantly at 0.1LC 50 group and 0.4LC 50 group, decresed at 0.8LC 50 group. Gene transcript results in this study were also similar to that described by (Seibt et al 2009), zebrafish were exposed to antipsychotic drugs, AChE transcription was up-regulated at high levels.…”

Section: Discussionsupporting

confidence: 90%

Toxic effects of HgCl2 on activities of SOD, AchE and relative expression of SOD, AChE, CYP1A1 of zebrafish

Wen

Yang

et al. 2014

Ecotoxicology

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In order to explore the impact of mercury on fish, zebrafish were exposed in various levels of HgCl2 and the superoxide dismutase (SOD), acetylcholinesterase (AChE) activities were measured after 1 and 7 days exposure. Muscle RNA was also extracted for semi-quantitative RT-PCR determination of the expression of AChE, CYP1A1, Cu/Zn-SOD. It indicated that 96 h-LC50 of HgCl2 to zebrafish is 244.06 µg L(-1). The AChE activity was decreased on 1st day and 7th day. The SOD activity was almost unchanged on 1st day, it showed a dose-response effect on 7th day. The expression of AChE was down-regulated on 1st day, it is consistent with the AChE activity, but the expression was showed a significant difference between exposed group and the control group on 7th day. The expression of CYP1A1 was decreased compared with the control group on 1st day. After 7 day exposure, the expression of CYP1A1 was up-regulated in 0.1LC(50) group, and down-regulated in 0.4LC(50) group, 0.8LC(50) group, showing a stimulation effect at low concentration and inhibition at high concentration. The expression of Cu/Zn-SOD was down-regulated on 1st day, also showing an effect of stimulation at low concentration and inhibition at high concentrations. Thus HgCl2 was highly toxic to zebrafish, both the enzymatic activities and the gene transcription were changed significantly. But the change of gene transcription is earlier than enzymes activities. It indicates that gene transcript can be used as an early warning for environmental risk assessment.

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Section: Discussionsupporting

confidence: 90%

Toxic effects of HgCl2 on activities of SOD, AchE and relative expression of SOD, AChE, CYP1A1 of zebrafish

Wen

Yang

et al. 2014

Ecotoxicology

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“…SZ patients underwent long-term drug treatment. Seibt et al [51] have studied the effect of the antipsychotic drugs haloperidol, olanzapine and sulpiride, prescribed for SZ, on the nucleotide hydrolysis in brain membranes of zebrafish. They found decreased ADPase activity in the presence of haloperidol and sulpiride but only at the highest concentration tested (250 μM).…”

Section: Discussionmentioning

confidence: 99%

Reduced striatal ecto-nucleotidase activity in schizophrenia patients supports the “adenosine hypothesis”

Aliagas

Villar-Menéndez

Sévigny

et al. 2013

Purinergic Signalling

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Schizophrenia (SZ) is a major chronic neuropsychiatric disorder characterized by a hyperdopaminergic state. The hypoadenosinergic hypothesis proposes that reduced extracellular adenosine levels contribute to dopamine D 2 receptor hyperactivity. ATP, through the action of ecto-nucleotidases, constitutes a main source of extracellular adenosine. In the present study, we examined the activity of ecto-nucleotidases (NTPDases, ecto-5′-nucleotidase, and alkaline phosphatase) in the postmortem putamen of SZ patients (n=13) compared with aged-matched controls (n=10). We firstly demonstrated, by means of artificial postmortem delay experiments, that ectonucleotidase activity in human brains was stable up to 24 h, indicating the reliability of this tissue for these enzyme determinations. Remarkably, NTPDase-attributable activity (both ATPase and ADPase) was found to be reduced in SZ patients, while ecto-5′-nucleotidase and alkaline phosphatase activity remained unchanged. In the present study, we also describe the localization of these ecto-enzymes in human putamen control samples, showing differential expression in blood vessels, neurons, and glial cells. In conclusion, reduced striatal NTPDase activity may contribute to the pathophysiology of SZ, and it represents a potential mechanism of adenosine signalling impairment in this illness.

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“…Moreover, studies from our laboratory demonstrated the presence of ectonucleotidase and ADA activities in zebrafish brain (Rico et al 2003;Rosemberg et al 2008;Senger et al 2004). Previous study showed that antipsychotics inhibited in vitro NTPDase activities in zebrafish brain (Seibt et al 2009), suggesting that these enzymes might be sensitive to these drugs. Thus, the purpose of this study was to investigate the acute effects of typical and atypical antipsychotics on ectonucleotidase and ADA activities in zebrafish brain and to evaluate their gene expression pattern analysis.…”

Section: Introductionmentioning

confidence: 73%

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

Seibt

Oliveira

Bogo

et al. 2015

Fish Physiol Biochem

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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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Antipsychotic drugs inhibit nucleotide hydrolysis in zebrafish (Danio rerio) brain membranes

Cited by 24 publications

References 38 publications

Toxic effects of HgCl2 on activities of SOD, AchE and relative expression of SOD, AChE, CYP1A1 of zebrafish

Toxic effects of HgCl2 on activities of SOD, AchE and relative expression of SOD, AChE, CYP1A1 of zebrafish

Reduced striatal ecto-nucleotidase activity in schizophrenia patients supports the “adenosine hypothesis”

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

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