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Adenosine receptor type 2a is differently modulated by nicotine in dorsal brainstem cells of Wistar Kyoto and spontaneously hypertensive rats

  • Basic Neurosciences, Genetics and Immunology-Original Article
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Abstract

Hypertension can result from neuronal network imbalance in areas of central nervous system that control blood pressure, such as the nucleus tractus solitarius (NTS). There are several neurotransmitters and neuromodulatory substances within the NTS, such as adenosine, which acts on purinoreceptors A2a (A2aR). The A2aR modulates neurotransmission in the NTS where its activation may induce decrease in blood pressure by different mechanisms. Nicotine is a molecule that crosses the hematoencephalic barrier and acts in several areas of central nervous system including the NTS, where it may interact with some neurotransmitter systems and contributes to the development of hypertension in subjects with genetic predisposition to this disease. In this study we first determined A2aR binding, protein, and mRNA expression in dorsomedial medulla oblongata of neonate normotensive (WKY) and spontaneously hypertensive rats (SHR). Subsequently, we analyzed the modulatory effects of nicotine on A2aR in cell culture in order to evaluate its possible involvement in the development of hypertension. Data showed a decreased A2aR binding and increased protein and mRNA expression in tissue sample and culture of dorsal brainstem from SHR compared with those from WKY rats at basal conditions. Moreover, nicotine modulated A2aR binding, protein, and mRNA expression in cells from both strains. Interestingly, nicotine decreased A2aR binding and increased protein levels, as well as, induced a differential modulation in A2aR mRNA expression. Results give us a clue about the mechanisms involved in the modulatory effects of nicotine on A2aR as well as hypothesize its possible contribution to the development of hypertension. In conclusion, we demonstrated that A2aR of SHR cells which differ from WKY and nicotine differentially modulates A2aR in dorsal brainstem cells of SHR and WKY.

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Acknowledgments

This study was supported by grants from Fundacao de Amparo à Pesquisa do Estado de Sao Paulo (FAPESP) and Conselho Nacional de Desenvolvimento e Tecnologia (CNPq). J. P. P. M received a mastering fellowship from Coordenacao de aperfeiçoamento de pessoal de nivel superior (CAPES).

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Authors and Affiliations

  1. Departamento de Fisiologia, Instituto de Biociencias, Universidade de Sao Paulo, Cidade Universitaria, Rua do Matao, Travessa 14, n. 321, São Paulo, SP, 05508-090, Brazil

    Joao Paulo Pontes de Matsumoto, Merari Fatima Ramires de Ferrari & Debora Rejane Fior-Chadi

  2. Departamento de Neurologia, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, Brazil

    Merari Fatima Ramires de Ferrari

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  1. Joao Paulo Pontes de Matsumoto
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  2. Merari Fatima Ramires de Ferrari
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  3. Debora Rejane Fior-Chadi
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Correspondence to Debora Rejane Fior-Chadi.

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de Matsumoto, J.P.P., de Ferrari, M.F.R. & Fior-Chadi, D.R. Adenosine receptor type 2a is differently modulated by nicotine in dorsal brainstem cells of Wistar Kyoto and spontaneously hypertensive rats. J Neural Transm 117, 799–807 (2010). https://doi.org/10.1007/s00702-010-0417-4

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  • DOI: https://doi.org/10.1007/s00702-010-0417-4

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