Imidazoline Receptors and Human Brain Disorders

Authors

  • JESÚS A. GARCÍA-SEVILLA,

    1. Laboratory of Neuropharmacology, Associate Unit of the Institute of Neurobiology Ramón y Cajal/CSIC, Department of Biology, University of the Balearic Islands, Cra. Valldemossa km 7.5, E-07071 Palma de Mallorca, Spain
    2. Department of Psychiatry, Medical School, University of Geneva, H.U.G., Belle-Idée, CH-1225 Chêne-Bourg, Switzerland
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  • PABLO V. ESCRIBÁ,

    1. Laboratory of Neuropharmacology, Associate Unit of the Institute of Neurobiology Ramón y Cajal/CSIC, Department of Biology, University of the Balearic Islands, Cra. Valldemossa km 7.5, E-07071 Palma de Mallorca, Spain
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  • JOSÉ GUIMÓN

    1. Department of Psychiatry, Medical School, University of Geneva, H.U.G., Belle-Idée, CH-1225 Chêne-Bourg, Switzerland
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Abstract

ABSTRACT: Major depression, opioid addiction, neurodegenerative diseases, and glial tumors are associated with disturbances of imidazoline receptors (IR) in the human brain. In depression, the level of a 45-kD IR protein (putative I1-IR) is increased in the brain of suicide victims (51%) and in platelets of depressed patients (40%). The density of platelet I1-IR ([125I]-p-iodoclonidine binding) is also increased in depression (135%). The 29/30-kD IR protein (putative I2B-IR) is downregulated (19%) in suicide victims in parallel with a reduction (40%) in the density of I2B-IR ([3H]idazoxan binding). Antidepressant drugs induce downregulation of 45-kD IR protein and I1-sites in platelets of depressed patients and upregulation of I2-sites in rat brain. The densities of I2B-IR and the related 29/30-kD IR protein are decreased (39% and 28%) in the brain of heroin addicts. The density of I2B-IR is increased in Alzheimer's disease (63%) and decreased in Huntington's disease (56%). Brain I2B-IR is not altered in Parkinson's disease. The level of I2-IR in glial tumors is increased (two fivefold) in parallel with the abundance of the related 29/30-kD IR protein (39%), whereas the level of 45-kD IR protein is decreased (39%). The possible functional relevance of these findings in the context of the pathogenesis of these disorders remains to be elucidated.

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