Boyajian C L, Loughlin S E, Leslie F M
J Pharmacol Exp Ther. 1987 Jun;241(3):1079-91.
Previous autoradiographic studies which have localized alpha-2 adrenoceptors within brain have used tritiated derivatives of clonidine and other alpha-2 adrenergic agonists. In the present study we have compared the autoradiographic distributions of binding sites labeled by two reportedly selective alpha-2 adrenoceptor antagonists, [3H]rauwolscine and [3H]idazoxan, in rat brain. The distribution of high affinity [3H]idazoxan binding sites differed markedly from that of high affinity [3H]rauwolscine sites throughout the neuraxis. The distribution of [3H]idazoxan binding sites paralleled closely that of [3H]clonidine sites, and corresponded to areas of noradrenergic innervation. Densest [3H]idazoxan labeling appeared over anterior olfactory nuclei, fundus striatum, septum, thalamus, hypothalamus, amygdala, entorhinal cortex, central gray, inferior colliculus, dorsal parabrachial nucleus, locus ceruleus and nucleus of the solitary tract. In contrast, much lower levels of [3H]rauwolscine labeling appeared over several areas which receive primarily dopaminergic innervation, and thus corresponded closely to [3H]spiroperidol binding distributions. Densest [3H]rauwolscine labeling appeared over nucleus caudate-putamen, nucleus accumbens, olfactory tubercle, Islands of Calleja, hippocampus, parasubiculum, basolateral amygdaloid nucleus and substantia nigra. In areas labeled by [3H]rauwolscine, computerized densitometric analysis of autoradiographic saturation curves revealed that the maximum binding values for [3H]idazoxan high affinity binding sites were consistently greater than those for high affinity [3H]rauwolscine sites. The pharmacological characterization of these two binding sites in the accompanying paper supports the present anatomical evidence that [3H]idazoxan labels a heterogenous population of alpha-2 adrenoceptor sites, one population of which is selectively labeled by [3H]rauwolscine.
以往将α₂肾上腺素能受体定位于脑内的放射自显影研究使用了可乐定和其他α₂肾上腺素能激动剂的氚化衍生物。在本研究中，我们比较了两种据报道具有选择性的α₂肾上腺素能拮抗剂[³H]育亨宾和[³H]咪唑克生在大鼠脑中标记的结合位点的放射自显影分布。在整个神经轴上，高亲和力[³H]咪唑克生结合位点的分布与高亲和力[³H]育亨宾位点的分布明显不同。[³H]咪唑克生结合位点的分布与[³H]可乐定位点的分布密切平行，并与去甲肾上腺素能神经支配区域相对应。最密集的[³H]咪唑克生标记出现在前嗅核、纹状体底、隔区、丘脑、下丘脑、杏仁核、内嗅皮质、中央灰质、下丘、臂旁背核、蓝斑和孤束核。相比之下，在几个主要接受多巴胺能神经支配的区域，[³H]育亨宾的标记水平要低得多，因此与[³H]螺哌啶醇的结合分布密切对应。最密集的[³H]育亨宾标记出现在尾状核 - 壳核、伏隔核、嗅结节、卡耶哈岛、海马、副下托、杏仁基底外侧核和黑质。在[³H]育亨宾标记的区域，对放射自显影饱和曲线进行计算机密度分析显示，[³H]咪唑克生高亲和力结合位点的最大结合值始终大于高亲和力[³H]育亨宾位点的最大结合值。随附论文中对这两个结合位点的药理学特征分析支持了目前的解剖学证据，即[³H]咪唑克生标记了α₂肾上腺素能受体位点的异质群体，其中一个群体被[³H]育亨宾选择性标记。
