Palacios J M, Hoyer D, Cortés R
Preclinical Research, Sandoz Ltd., Basle, Switzerland.
Brain Res. 1987 Sep 1;419(1-2):65-75. doi: 10.1016/0006-8993(87)90569-5.
We have used membrane binding assays and in vitro autoradiographic techniques to study the characteristics and distribution of alpha 1-adrenoceptors in the brain of the rat, mouse, guinea pig, cat, pig, monkey and man. 125I-BE 2254 was used as ligand. The binding characteristics of alpha 1-adrenoceptors in the cortex of the rat and pig and the human cortex and hippocampus were fully comparable as shown by the binding profile of a series of alpha 1-adrenergic compounds. Differences were, however, seen in the densities of sites in human and rat hippocampus. Contrasting with the similarities seen in the pharmacological characteristics of alpha 1-adrenoceptors in the brain of several mammals, autoradiographic results showed dramatic differences in the regional distribution of brain alpha 1-adrenoceptors. While the thalamus and cortex were rich in alpha 1-sites in all the species investigated, differences in the nuclear and laminar distributions were seen between rodents and primates. One of the most important differences was the high density of alpha 1-adrenoceptors in the human and monkey hippocampus, mainly in the CA3, CA4 and dentate gyrus, while in all the other species investigated, the hippocampal formation was poor in these sites. These results suggest that, while alpha 1-adrenoceptors appear to be similar in their pharmacology, their distribution differs among these 6 mammals. Thus, different patterns of central activity can be expected from alpha 1-adrenergic drugs in the rodent and in the primate and man.
我们运用膜结合分析法和体外放射自显影技术，研究了大鼠、小鼠、豚鼠、猫、猪、猴及人类大脑中α1-肾上腺素能受体的特征与分布。以125I-BE 2254作为配体。一系列α1-肾上腺素能化合物的结合图谱显示，大鼠和猪的皮质以及人类皮质和海马体中α1-肾上腺素能受体的结合特征完全可比。然而，人类和大鼠海马体中受体位点的密度存在差异。与几种哺乳动物大脑中α1-肾上腺素能受体药理学特征的相似性形成对比的是，放射自显影结果显示大脑α1-肾上腺素能受体的区域分布存在显著差异。在所研究的所有物种中，丘脑和皮质富含α1-位点，但啮齿动物和灵长类动物在核层和板层分布上存在差异。最重要的差异之一是人类和猴海马体中α1-肾上腺素能受体密度较高，主要集中在CA3、CA4和齿状回，而在其他所有研究物种中，海马结构在这些位点的受体较少。这些结果表明，虽然α1-肾上腺素能受体的药理学特性似乎相似，但其在这6种哺乳动物中的分布有所不同。因此，预计α1-肾上腺素能药物在啮齿动物、灵长类动物和人类中的中枢活动模式会有所不同。
