Characterization and Regional Distribution of ?2-Adrenoceptors in Postmortem Human Brain Using the Full Agonist [3H]UK 14304

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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.degree. Cwas 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 .simeq. yohimbine .simeq. oxymetazoline .simeq. clonidine > phentolamine .simeq.(-)-noradrenaline > phenylephrine > (.+-.)-adrenaline .gtoreq. corynanthine > prazosin .gtoreq. (.+-.)-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]UK14304 was not affected by age, sex or postmortem delay. [3H]UK 14304 should be a useful tool to assess brain .alpha.2-adrenoceptor density in a variety of neuropsychiatric disorders.