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Opposite Age‐Dependent Changes of α2A‐Adrenoceptors and Nonadrenoceptor [3H]Idazoxan Binding Sites (I2‐Imidazoline Sites) in the Human Brain: Strong Correlation of I2 with Monoamine Oxidase‐B Sites

Abstract: In the postmortem human brain (27 specimens of frontal cortex, Brodmann area 9), the specific binding of the antagonists [3H]RX 821002 (2‐methoxyidazoxan) to α2A‐adrenoceptors and that of [3H]idazoxan to l2‐imidazo‐line sites (a nonadrenoceptor mitochondrial site) were determined in parallel to study the effect of aging (range, 4–89 years) on both brain proteins. The density of α2A‐adrenoceptors and age were negatively correlated (r=‐0.71; p < 0.001). In contrast, the density of l2‐imidazo‐line sites was positively correlated with aging (r= 0.59; p < 0.005). The ratio of receptor densities (α2A/l2) also showed a marked negative correlation with age (r=‐0.76; p < 0.001). In an age‐selected group (range, 10–89 years), the density of monoamine oxidase (MAO)‐B sites labeled by [3H]Ro 19–6327 (lazabemide) also showed a positive correlation with age (r= 0.80; p < 0.005). In these subjects, the density of l2‐imidazoline sites correlated well with the density of MAO‐B sites (r= 0.70; p < 0.005). The ratio of the density of these sites (MAO‐B/l2) did not correlate with the age of the subject at death (r=‐0.15). In the human frontal cortex, idazoxan displayed very low affinity (Ki= 89 μM) against the binding of [3H]Ro 19–6327 to MAO‐B, which discounted a direct interaction of [3H]idazoxan with the active center of the enzyme and indicated that the l2‐imidazoline site cannot be identified with MAO‐B. However, l2‐imidazoline sites and MAO‐B show a clear coexpression not only in the human frontal cortex during the process of aging, but also in various brain regions of the human and rat brains. It is suggested that the l2‐imidazoline site has a specific location on glial (astrocyte) cells.