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 I-1-IR) is increased in the brain of suicide victims (51 %) and in platelets of depressed patients (40 %). The density of platelet I-1-IR ([I-125]-p-iodoclonidine binding) is also increased in depression (135%). The 29/30-kD IR protein (putative I-2B-IR) is downregulated (19%) in suicide victims in parallel with a reduction (40%) in the density of I2B-IR ([H-3]idazoxan binding). Antidepressant drugs induce downregulation of 45-kD IR protein and I-1-sites in platelets of depressed patients: and upregulation of I-2-sites in rat brain. The densities of I-2B-IR and the related 29/30-kD IR protein are decreased (39% and 28%) in the brain of heroin addicts. The density of I-2B-IR is increased in Alzheimer's disease (63%) and decreased in Huntington's disease (56%). Brain I-2B-IR is not altered in Parkinson's disease. The level of I-2-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 bf 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.