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Physiological level of norepinephrine increases adenine nucleotides hydrolysis in rat blood serum

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Abstract

Extracellular adenosine 5′-triphosphate (ATP) and its breakdown products, adenosine 5′-diphosphate (ADP) and adenosine, have significant effects on a variety of biological processes. NTPDase enzymes, responsible for adenine nucleotides hydrolysis, are considered the major regulators of purinergic signaling in the blood. Previous work by our group demonstrated that ATP and ADP hydrolysis in rat blood serum are higher during the dark (activity) phase compared to the light (rest) phase. In nocturnal animals (e.g., rats), important physiological changes occur during the dark phase, such as increased circulating levels of melatonin, corticosterone, and norepinephrine (NE). This study investigated the physiological effects, in vivo and in vitro, of melatonin, dexamethasone, and NE upon nucleotides hydrolysis in rat blood serum. For in vivo experiments, the animals received a single injection of saline (control), melatonin (0.05 mg/kg), dexamethasone (0.1 mg/kg), or NE (0.03 mg/kg). For in vitro experiments, melatonin (1.0 nM), dexamethasone (1.0 μM), or NE (1.0 nM) was added directly to the reaction medium with blood serum before starting the enzyme assay. The results demonstrated that ATP and ADP hydrolysis in both in vitro and in vivo experiments were significantly higher with NE treatment compared to control (in vitro: ATP = 36.63%, ADP = 22.43%, P < 0.05; in vivo: ATP = 44.1%, ADP = 37.28%, P < 0.001). No significant differences in adenine nucleotides hydrolysis were observed with melatonin and dexamethasone treatments. This study suggests a modulatory role of NE in the nucleotidases pathway, decreasing extracellular ATP and ADP, and suggests that NE might modulate its own release by increasing the activities of soluble nucleotidases.

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Acknowledgments

This work was supported by the following Brazilian Funding Agencies: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; Dr. I.L.S. Torres), Graduate Research Group (GPPG) at Hospital de Clínicas de Porto Alegre (Dr. I.L.S. Torres, Grant no. 08-150), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).

Conflict of interest

The authors declare that they have no conflict of interest. The authors alone are responsible for the content and writing of the paper.

Ethical standard

All experiments were performed in accordance with the Brazilian Community’s Council Directive of October 8, 2008 (Law No. 11.794) with all efforts made to minimize animal suffering and using the number of animals necessary to produce reliable scientific data. The experimental protocol was approved by the Ethics Committee at the Hospital de Clínicas de Porto Alegre.

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Authors and Affiliations

  1. Laboratório de Farmacologia da Dor, Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, 90050-170, Brazil

    Bernardo Carraro Detanico, Joanna Ripoll Rozisky & Iraci Lucena da Silva Torres

  2. Programa de Pós-Graduação em Medicina: Ciências Médicas, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2400, Porto Alegre, Rio Grande do Sul, 90035-003, Brazil

    Bernardo Carraro Detanico, Joanna Ripoll Rozisky, Ana Maria Oliveira Battastini & Iraci Lucena da Silva Torres

  3. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, 90035-003, Brazil

    Ana Maria Oliveira Battastini

  4. Unidade de Experimentação Animal, Grupo de Pesquisa e Pós-Graduação do Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, 90035-003, Brazil

    Bernardo Carraro Detanico, Joanna Ripoll Rozisky & Iraci Lucena da Silva Torres

  5. Departamento de Farmacologia, ICBS, UFRGS, Rua Sarmento Leite 500, sala 202, Cep 90050-170, Porto Alegre, Rio Grande do Sul, Brazil

    Iraci Lucena da Silva Torres

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  1. Bernardo Carraro Detanico
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  2. Joanna Ripoll Rozisky
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  3. Ana Maria Oliveira Battastini
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  4. Iraci Lucena da Silva Torres
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Corresponding author

Correspondence to Iraci Lucena da Silva Torres.

Additional information

Bernardo Carraro Detanico and Joanna Ripoll Rozisky are the first authors of this study.

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Detanico, B.C., Rozisky, J.R., Battastini, A.M.O. et al. Physiological level of norepinephrine increases adenine nucleotides hydrolysis in rat blood serum. Purinergic Signalling 7, 373–379 (2011). https://doi.org/10.1007/s11302-011-9253-8

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