title: Characterization and regional distribution of alpha 2-adrenoceptors in postmortem human brain using the full agonist [3H]UK 14304.
abstract: The full agonist [3H]UK 14304 [5-bromo-6-(2-imidazolin-2-yl-amino)-quinoxaline] was used to characterize alpha 2-adrenoceptors in postmortem human brain. The binding at 25 degrees C was rapid (t1/2, 4.6 min) and reversible (t1/2, 14.1 min), and the KD determined from the kinetic studies was 0.48 nM. In frontal cortex, the rank order of potency of adrenergic drugs competing with [3H]UK 14304 or [3H]clonidine showed the specificity for an alpha 2A-adrenoceptor: UK 14304 approximately equal to yohimbine approximately equal to oxymetazoline approximately equal to clonidine greater than phentolamine approximately equal to (-)-adrenaline greater than idazoxan approximately equal to (-)-noradrenaline greater than phenylephrine greater than (+/-)-adrenaline much greater than corynanthine greater than prazosin much greater than (+/-)-propranolol. GTP induced a threefold decrease in the affinity of [3H]UK 14304, with no alteration in the maximum number of binding sites, suggesting that the radioligand labelled the high-affinity state of the alpha 2-adrenoceptor. In the frontal cortex, analyses of saturation curves indicated the existence of a single population of noninteracting sites for [3H]UK 14304 (KD = 0.35 +/- 0.13 nM; Bmax = 74 +/- 9 fmol/mg of protein). In other brain regions (hypothalamus, hippocampus, cerebellum, brainstem, caudate nucleus, and amygdala) the Bmax ranged from 68 +/- 7 to 28 +/- 4 fmol/mg of protein. No significant changes in the KD values were found in the different regions examined. The binding of [3H]UK 14304 was not affected by age, sex or postmortem delay.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of the Basque Country, Leioa, Bizkaia, Spain.
authors.forename: J J
authors.initials: JJ
authors.lastname: Meana
authors.forename: F
authors.initials: F
authors.lastname: Barturen
authors.forename: J A
authors.initials: JA
authors.lastname: García-Sevilla
mesh_terms: D000328:Adult; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D000068438:Brimonidine Tartrate; D005260:Female; D006801:Humans; D008297:Male; D011810:Quinoxalines / Q000493:pharmacokinetics; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D014018:Tissue Distribution; D014316:Tritium
chemical_list: D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D014316:Tritium; D000068438:Brimonidine Tartrate