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Adenosine, dopamine and serotonin receptors imbalance in lymphocytes of Lesch-Nyhan patients

  • Original Article
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Lesch-Nyhan disease (LND) is caused by complete deficiency of the hypoxanthine-guanine phosphoribosyltransferase enzyme. It is characterized by overproduction of uric acid, jointly with severe motor disability and self-injurious behaviour which physiopathology is unknown. These neurological manifestations suggest a dysfunction in the basal ganglia, and three neurotransmitters have been implicated in the pathogenesis of the disease: dopamine, adenosine and serotonin. All of them are implicated in motor function and behaviour, and act by binding to specific G-protein coupled receptors in the synaptic membrane where they seem to be integrated through receptor–receptor interactions. In this work we have confirmed at protein level the previously reported increased expression of DRD5 and the variably aberrant expression of ADORA2A, in LND PBL respect to control PBL. We have also described, for the first time, a decreased expression and protein level of 5-HTR1A in LND PBL respect to control PBL. If these results were confirmed in the Lesch-Nyhan patients basal ganglia cells, this would support the hypothesis that pathogenesis of neurological manifestations of Lesch-Nyhan patients may be related to an imbalance of neurotransmitters, rather than to the isolated disturbance of one of the neurotransmitters, and this fact should be taken into account in the design of pharmacologic treatment for their motor and behavioural disturbances.

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Acknowledgements

This work was supported by a Grant from Fondo de Investigaciones Sanitarias (Health Research Fund, FIS) 08/0009. Garcia MG has a contract from the Fundacion de Investigacion Biomédica del Hospital la Paz (Biomedical Research Foundation of the La Paz Hospital, FIBHULP).

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Authors and Affiliations

  1. Clinical Biochemistry Department, Metabolic Vascular Unit, IdiPaz, La Paz University Hospital, Madrid, Spain

    Marta G. García & Rosa J. Torres

  2. Internal Medicine Department, Metabolic Vascular Unit, IdiPaz, La Paz University Hospital, Madrid, Spain

    Juan G. Puig

  3. Servicio de Bioquímica, Edificio Laboratorio, Hospital Universitario La Paz, Paseo de la Castellana, 261, 28046, Madrid, Spain

    Rosa J. Torres

Authors
  1. Marta G. García
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  2. Juan G. Puig
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  3. Rosa J. Torres
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Corresponding author

Correspondence to Rosa J. Torres.

Additional information

Communicated by: Bruce A. Barshop

Competing interest: None declared.

Marta G. García, Juan G. Puig and Rosa J. Torres contribute equally.

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García, M.G., Puig, J.G. & Torres, R.J. Adenosine, dopamine and serotonin receptors imbalance in lymphocytes of Lesch-Nyhan patients. J Inherit Metab Dis 35, 1129–1135 (2012). https://doi.org/10.1007/s10545-012-9470-5

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  • DOI: https://doi.org/10.1007/s10545-012-9470-5

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