Up-regulation of adenosine A1 receptors in frontal cortex from Pick's disease cases

Authors

  • José Luis Albasanz,

    1. Departamento de Química Inorgánica, Orgánica y Bioquímica, Facultad de Químicas, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha, Ciudad Real, Spain
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  • Agustín Rodríguez,

    1. Departamento de Biología Celular y Anatomía Patológica, Facultad de Medicina, Universidad de Barcelona, campus de Bellvitge, Hospitalet de Llobregat, Spain
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  • Isidro Ferrer,

    1. Departamento de Biología Celular y Anatomía Patológica, Facultad de Medicina, Universidad de Barcelona, campus de Bellvitge, Hospitalet de Llobregat, Spain
    2. Instituto de Neuropatología, Servicio de Anatomía Patológica, IDIBELL-Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Spain
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  • Mairena Martín

    1. Departamento de Química Inorgánica, Orgánica y Bioquímica, Facultad de Químicas, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha, Ciudad Real, Spain
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Dr Mairena Martín, Área de Bioquímica, Facultad de Ciencias Químicas, Avenida Camilo José Cela, 10, 13071 Ciudad Real, Spain.
E-mail: Mairena.Martin@uclm.es

Abstract

The adenosine A1 receptor (A1R)–adenylyl cyclase (AC) pathway was studied in post-mortem human frontal and occipital cortex from Pick's disease (PiD) cases and age-matched nondemented controls. In frontal cortex, the main brain area affected in PiD, A1Rs, determined by radioligand binding, Western blotting and real-time PCR assays, were significantly increased in PiD samples, suggesting up-regulation of this receptor. AC activity was determined in basal and stimulated conditions via stimulatory guanine nucleotide binding proteins (Gs) using GTP, or directly with forskolin. Basal AC activity was reduced in brains from PiD cases. This agrees with the decrease in AC type I (AC I) level detected by Western blotting. However, inhibition of forskolin-stimulated AC activity by a selective A1R agonist was significantly increased in brains from PiD. In occipital cortex, adenosine A1R numbers were similar in control and PiD cases, and no significant differences were found in A1R-mediated AC inhibition. These results show that the adenosine A1R–AC transduction pathway is specifically up-regulated and sensitized in frontal cortex brain in PiD.

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