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Characterization and Regional Distribution of α 2 ‐Adrenoceptors in Postmortem Human Brain Using the Full Agonist [ 3 H]UK 14304
Author(s) -
Meana J. Javier,
Barturen Fernando,
GarcíaSevilla Jesús A.
Publication year - 1989
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1989.tb01868.x
Subject(s) - oxymetazoline , prazosin , chemistry , nucleus accumbens , agonist , endocrinology , medicine , population , antagonist , biology , receptor , biochemistry , environmental health
The full agonist [ 3 H]UK 14304 [5‐bromo‐6‐(2‐im‐idazolin‐2‐yl‐amino)‐quinoxaline] was used to characterize α 2 ‐adrenoceptors in postmortem human brain. The binding at 25°C was rapid ( t 1/2 , 4.6 min) and reversible ( t 1/2 , 14.1 min), and the K d determined from the kinetic studies was 0.48 n M In frontal cortex, the rank order of potency of adrenergic drugs competing with [ 3 H]UK 14304 or [ 3 H]clonidine showed the specificity for an α 2A ‐adrenoceptor: UK 14304 ≅ yohimbine ≅ oxymetazoline ≅ clonidine > phentolamine ≅ (–)‐adrenaline > idazoxan ≅ (–) ‐noradrenaline > phenylephrine > (±)‐adrenaline ≫ corynanthine > prazosin ≫ (±)‐propranolol. GTP induced a threefold decrease in the affinity of [ 3 H]UK 14304, with no alteration in the maximum number of binding sites, suggesting that the radioligand labelled the high‐affinity state of the α 2 ‐adreno‐ceptor. In the frontal cortex, analyses of saturation curves indicated the existence of a single population of noninter‐acting sites for [ 3 H]UK 14304 (K d = 0.35 ± 0.13 n M ; B max = 74 ± 9 fmol/mg of protein). In other brain regions (hypothalamus, hippocampus, cerebellum, brainstem, caudate nucleus, and amygdala) the B max ranged from 68 ± 7 to 28 ± 4 fmol/mg of protein. No significant changes in the K d values were found in the different regions examined. The binding of [ 3 H]UK 14304 was not affected by age, sex or postmortem delay. [ 3 H]UK 14304 should be a useful tool to assess brain α 2 ‐adrenoceptor density in a variety of neuropsychiatric disorders.