Relationships between beta- and alpha(2)-adrenoceptors and G coupling proteins in the human brain: effects of age and suicide

Interactions between brain alpha (2)- and beta -adrenoceptors are of intere st in physiological (aging) and pathological (major depression) processes i nvolving both receptors. In this study, total beta -adrenoceptors and beta (1/2)-subtypes were quantitated in postmortem human brains to investigate t heir relationships with alpha (2A)-adrenoceptors and specific G proteins du ring the process of aging and in brains of suicide victims. Analysis of [H- 3]CGP12177 binding, in the presence of CGP20712A (beta (1)-antagonist), ind icated that the predominant beta -adrenoceptor in the frontal cortex is the beta (1)-subtype (65-75%). The density of total beta- (r = -0.60, n = 43) or beta (1)-adrenoceptors (r = -0.78, n = 72), but not the beta (2)-subtype , declined with aging (3-80 years). The density of total beta- or beta (1)- adrenoceptors, but not the beta (2)-subtype, correlated with the number of alpha (2)-adrenoceptors quantitated in the same brains with the agonist [H- 3]UK14304 (r = 0.71-0.81) or the antagonist [H-3]RX821002 (r = 0.61-0.66). Interestingly, the ratios alpha (2)/beta- or alpha (2)/beta (1)-adrenocepto rs did not correlate with the age of the subject at death, indicating that the proportion of alpha (2)/beta -adrenoceptors in brain remains rather con stant during the process of aging. The density of beta -adrenoceptors corre lated with the immunodensity of G alphas (r = 0.55) and G beta (r = 0.61) p roteins, and that of alpha (2)-adrenoceptors with those of G alphai(1/2) (r = 0.88) and G beta (r = 0.65). In brains of suicides, compared to controls , the ratio between alpha (2)- and beta- or beta (1)-adrenoceptors (alpha ( 2)-full agonist sites/beta -sites) was greater (1.3- to 2.0-fold; P < 0.05) . The results demonstrate a close interdependence between brain <alpha>(2)- and beta -adrenoceptors during aging, and in brains of suicides. The quant itation of the alpha (2A)/beta -adrenoceptor ratio could represent a releva nt neurochemical index in the study of brain pathologies in which both rece ptors are involved. (C) 2001 Elsevier Science B.V. All rights reserved.