Relationships between β- and α2-adrenoceptors and G coupling proteins in the human brain: effects of age and suicide |
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Authors: | Magdalena Sastre, Jos Guim n,Jesú s A. Garcí a-Sevilla |
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Affiliation: | a Laboratory of Neuropharmacology, Associate Unit of the Institute Cajal/CSIC, Department of Biology, University of the Balearic Islands, Cra. Valldemossa Km 7.5, E-07071 Palma de Mallorca, Spain;b Clinical Research Unit, Department of Psychiatry, University of Geneva, H.U.G., Belle-Idée, CH-1225 Chêne-Bourg, Switzerland |
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Abstract: | Interactions between brain α2- and β-adrenoceptors are of interest in physiological (aging) and pathological (major depression) processes involving both receptors. In this study, total β-adrenoceptors and β1/2-subtypes were quantitated in postmortem human brains to investigate their relationships with α2A-adrenoceptors and specific G proteins during the process of aging and in brains of suicide victims. Analysis of [3H]CGP12177 binding, in the presence of CGP20712A (β1-antagonist), indicated that the predominant β-adrenoceptor in the frontal cortex is the β1-subtype (65–75%). The density of total β- (r=−0.60, n=44) or β1-adrenoceptors (r=−0.78, n=22), but not the β2-subtype, declined with aging (3–80 years). The density of total β- or β1-adrenoceptors, but not the β2-subtype, correlated with the number of α2-adrenoceptors quantitated in the same brains with the agonist [3H]UK14304 (r=0.71–0.81) or the antagonist [3H]RX821002 (r=0.61–0.66). Interestingly, the ratios α2/β- or α2/β1-adrenoceptors did not correlate with the age of the subject at death, indicating that the proportion of α2/β-adrenoceptors in brain remains rather constant during the process of aging. The density of β-adrenoceptors correlated with the immunodensity of Gαs (r=0.55) and Gβ (r=0.61) proteins, and that of α2-adrenoceptors with those of Gαi1/2 (r=0.88) and Gβ (r=0.65). In brains of suicides, compared to controls, the ratio between α2- and β- or β1-adrenoceptors (α2-full agonist sites/β-sites) was greater (1.3- to 2.0-fold; P<0.05). The results demonstrate a close interdependence between brain α2- and β-adrenoceptors during aging, and in brains of suicides. The quantitation of the α2A/β-adrenoceptor ratio could represent a relevant neurochemical index in the study of brain pathologies in which both receptors are involved. |
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Keywords: | β -Adrenoceptor α 2A-Adrenoceptor G coupling protein Human brain Aging Suicide |
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