Imidazoline receptors and human brain disorders.
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.
Institute of Neurobiology Ramón y Cajal/CSIC, Department of Biology, University of the Balearic Islands, Palma de Mallorca, Spain.
J A
JA
García-Sevilla
P V
PV
Escribá
J
J
Guimón
D000437:Alcoholism / Q000378:metabolism; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D001927:Brain Diseases / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism; D003866:Depressive Disorder / Q000378:metabolism; D006801:Humans; D054755:Imidazoline Receptors; D019636:Neurodegenerative Diseases / Q000378:metabolism; D009293:Opioid-Related Disorders / Q000378:metabolism; D051381:Rats; D011955:Receptors, Drug / Q000235:genetics / Q000378:metabolism*; D013405:Suicide
D054755:Imidazoline Receptors; D011955:Receptors, Drug