title: Characterization of [125I]HEAT binding to alpha 1-receptors in human brain: assessment in aging and Alzheimer's disease.
abstract: The binding of [125I]2-(beta-4-hydroxyphenylethylamino-ethyltetralone ([ 125I]HEAT), an alpha 1-adrenergic receptor antagonist, to human brain membranes was characterized and the binding assessed in tissue from subjects with Alzheimer's disease (AD) and aging controls. Under Na+-K+ phosphate buffer conditions, [125I]HEAT bound to a single class of binding sites in prefrontal cortex (Brodmann area 10) with a Kd of about 120 pM. High binding capacities of [125I]HEAT were evident in the hippocampus and neocortex but were low in subcortical areas and cerebral microvessels comparable to the regional distribution of [3H]prazosin binding reported previously. Displacement of [125I]HEAT by various adrenergic drugs was consistent with its binding to alpha 1-adrenergic receptors. The specific binding was not affected by postmortem delay between death and freezing of tissue at autopsy. There was no correlation of [125I]HEAT binding with age of subjects. In AD subjects, the binding was significantly decreased in prefrontal cortex by about 25% but not changed in hippocampus, putamen or cerebellum compared to age-matched controls. The reduced binding of [125I]HEAT in prefrontal cortex may reflect a region-specific change in alpha 1-adrenergic receptors associated with neuronal loss in AD.
authors.affiliation: Department of Neurology, Case Western Reserve School of Medicine, Cleveland, OH 44106.
authors.forename: R N
authors.initials: RN
authors.lastname: Kalaria
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010627:Phenethylamines / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D044024:Tetralones
chemical_list: D010627:Phenethylamines; D011942:Receptors, Adrenergic, alpha; D044024:Tetralones; C010652:BE 2254