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 alpha 2A-adrenoceptors and that of [3H]idazoxan to I2-imidazoline 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 alpha 2A-adrenoceptors and age were negatively correlated (r = -0.71; p < 0.001). In contrast, the density of I2-imidazoline sites was positively correlated with aging (r = 0.59; p < 0.005). The ratio of receptor densities (alpha 2A/I2) 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 I2-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/I2) 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 microM) 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 I2-imidazoline site cannot be identified with MAO-B.(ABSTRACT TRUNCATED AT 250 WORDS)