Winzer-Serhan U H, Raymon H K, Broide R S, Chen Y, Leslie F M
Department of Pharmacology, College of Medicine, University of California, Irvine 92717, USA.
Neuroscience. 1997 Jan;76(1):261-72. doi: 10.1016/s0306-4522(96)00369-7.
The distributions of alpha 2C adrenoceptor messenger RNA and high-affinity [3H]rauwolscine binding sites were characterized in developing rat brain. Using in situ hybridization with 35S-labeled riboprobes directed against the third intracellular loop, alpha 2C messenger RNA expression appeared in an adult-like pattern during the first and second postnatal weeks, in the anterior olfactory nucleus, caudate-putamen, olfactory tubercles, islands of Calleja and hippocampus, following the time-course of maturation of these structures. Only in the cerebellum was alpha 2C messenger RNA transiently expressed during the critical period of granule cell development. High-affinity [3H]rauwolscine binding sites were detected using receptor autoradiography and revealed a similar spatial and temporal time-course of appearance during rat brain development. The highest numbers of binding sites were detected in the olfactory tubercles and islands of Calleja, and moderate numbers in the anterior olfactory nucleus, caudate-putamen and hippocampus. Like alpha 2C messenger RNA expression, high-affinity [3H]rauwolscine binding sites were transiently expressed in the cerebellum. In some areas (e.g., the substantia nigra), [3H]rauwolscine binding sites were detected even though alpha C2 messenger RNA expression was absent. The strong spatial and temporal correspondence between messenger RNA expression and radioligand binding supports the conclusion that [3H]rauwolscine selectively labels alpha 2C adrenoceptors in the rat brain. The developmental pattern which was observed is in marked contrast to the early, transient expression of the alpha 2A adrenoceptor. Thus, the alpha 2A and alpha 2C receptor types may serve distinct functional roles in the developing brain.
在发育中的大鼠脑内,对α2C肾上腺素能受体信使核糖核酸(mRNA)和高亲和力[3H]萝芙木碱结合位点的分布进行了表征。使用针对第三个细胞内环的35S标记核糖探针进行原位杂交,α2C信使核糖核酸的表达在出生后的第一周和第二周呈现出类似成年的模式,在前嗅核、尾状核-壳核、嗅结节、Calleja岛和海马体中,随着这些结构的成熟时间进程而出现。仅在小脑,α2C信使核糖核酸在颗粒细胞发育的关键时期短暂表达。使用受体放射自显影检测到高亲和力[3H]萝芙木碱结合位点,并揭示了其在大鼠脑发育过程中出现的类似空间和时间进程。在嗅结节和Calleja岛中检测到最高数量的结合位点,在前嗅核、尾状核-壳核和海马体中检测到中等数量的结合位点。与α2C信使核糖核酸表达一样,高亲和力[3H]萝芙木碱结合位点在小脑中短暂表达。在一些区域(如黑质),即使没有αC2信使核糖核酸表达,也检测到了[3H]萝芙木碱结合位点。信使核糖核酸表达与放射性配体结合之间强烈的空间和时间对应关系支持了[3H]萝芙木碱在大鼠脑中选择性标记α2C肾上腺素能受体的结论。观察到的发育模式与α2A肾上腺素能受体的早期短暂表达形成鲜明对比。因此,α2A和α2C受体类型在发育中的大脑中可能发挥不同的功能作用。