title: Density of alpha-2A adrenoceptors and Gi proteins in the human brain: ratio of high-affinity agonist sites to antagonist sites and effect of age.
abstract: In the postmortem human brain, the specific binding of the agonists [3H]clonidine and [3H]bromoxidine ([3H]UK14034) and of the antagonist [3H]2-methoxyidazoxan (RX821002) and inhibition by l-epinephrine of [3H]RX821002 binding were determined in parallel to quantify the fractions of high (RH)- and low-affinity (RL) agonist sites of alpha-2A adrenoceptors and to investigate the association of these inhibitory receptors with various regulatory Gi proteins and the effect of aging. In the frontal cortex, the density of RH with [3H]clonidine was not different from that with [3H]UK14304 and the ratio of Bmax values in the same subjects was 0.88 +/- 0.05 (n = 39). The inhibition of [3H] RX821002 binding by l-epinephrine allowed the resolution and quantitation of the RH and RL with similar values to those obtained in saturation experiments. The simultaneous analysis and computer modeling of competition and saturation experiments performed in the same subjects indicated that a high proportion of alpha-2A adrenoceptors exist in the RH conformation (70-80%). The density of alpha-2A adrenoceptors (Bmax for [3H]agonist and [3H]antagonist binding) and age (range, 4-89 years) were negatively correlated (r = -.60, n = 39, P < .001). However, only the density of RH declined with aging (r = -.68, n = 38, P < .001); that of RL did not appear to be age related (r = -.26, n = 37, P > .05).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Fundamental Biology and Health Sciences, University of the Balearic Islands, Palma de Mallorca, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Sastre
authors.forename: J A
authors.initials: JA
authors.lastname: García-Sevilla
mesh_terms: D000293:Adolescent; D000316:Adrenergic alpha-Agonists / Q000378:metabolism*; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D001665:Binding Sites; D001923:Brain Chemistry; D000068438:Brimonidine Tartrate; D002648:Child; D002675:Child, Preschool; D003000:Clonidine / Q000378:metabolism; D004146:Dioxanes / Q000378:metabolism; D005260:Female; D019204:GTP-Binding Proteins / Q000032:analysis*; D006801:Humans; D019329:Idazoxan / Q000031:analogs & derivatives; D008297:Male; D008875:Middle Aged; D011810:Quinoxalines / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000032:analysis*
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D000068438:Brimonidine Tartrate; C058525:2-methoxyidazoxan; D019204:GTP-Binding Proteins; D003000:Clonidine; D019329:Idazoxan