Opposite age-dependent changes of alpha 2A-adrenoceptors and nonadrenoceptor [3H]idazoxan binding sites (I2-imidazoline sites) in the human brain: strong correlation of I2 with monoamine oxidase-B sites.
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)
Sastre
M
M
Department of Fundamental Biology and Health Sciences, University of the Balearic Islands, Palma de Mallorca, Spain.
García-Sevilla
J A
JA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D004146:Dioxanes / Q000378:metabolism*; D005260:Female; D006801:Humans; D019329:Idazoxan / Q000031:analogs & derivatives; D054755:Imidazoline Receptors; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000378:metabolism*; D010848:Picolinic Acids / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011955:Receptors, Drug / Q000378:metabolism*; D013844:Thiazoles / Q000378:metabolism
D004146:Dioxanes; D054755:Imidazoline Receptors; D010848:Picolinic Acids; D011942:Receptors, Adrenergic, alpha; D011955:Receptors, Drug; D013844:Thiazoles; C063456:Ro 41-1049; C059303:lazabemide; C058525:2-methoxyidazoxan; D008995:Monoamine Oxidase; D019329:Idazoxan