Kurihara M, Ochi A, Kawaguchi T, Niwa M, Kataoka Y, Mori K
Department of Neurosurgery, Nagasaki University School of Medicine, Japan.
Neurosurgery. 1990 Aug;27(2):275-81. doi: 10.1097/00006123-199008000-00017.
Localization and characterization of endothelin receptors in surgical specimens of human gliomas (6 benign astrocytomas and 7 glioblastomas multiforme) and in normal human cortices were studied using quantitative receptor autoradiographic methods. Low numbers of [125I]endothelin-1 [( 125I]ET-1) binding sites were detected in the gray matter of the human frontal cortex, with little binding in the white matter. Conversely, relatively high numbers of [125I]ET-1 binding sites were homogeneously present in tissue sections derived from astrocytomas, whereas higher numbers of [125I]ET-1 binding sites were heterogeneously located on groups of cells with a pseudopalisading appearance and pleomorphic astrocytes in glioblastoma multiforme. Necrotic areas within the tissue sections derived from glioblastoma were devoid of binding. Binding of [125I]ET-1 to gliomas and normal gray matter was specific. Unlabeled ET-1 and its natural analogs (ET-2 and ET-3) inhibited the binding of [125I]ET-1 to these lesions in a concentration-dependent manner and with similar high potencies. Possibly related substances, such as ion channel regulators (omega-conotoxin, apamin, and tetrodotoxin), a Ca2+ channel blocker (nicardipine), and growth factors (epidermal growth factor and insulin-like growth factor I), did not affect the binding to tissue sections derived from gliomas or from normal frontal cortices. Scatchard analysis revealed the presence of a single class and high-affinity binding sites for endothelin in normal cortex and in gliomas. There was no significant difference in the binding affinities: dissociation constants (Kd) were 2.1 +/- 0.5 nM in 6 astrocytomas, 2.5 +/- 0.4 nM in 7 glioblastomas, and 1.4 and 1.5 nM in two normal cortices.(ABSTRACT TRUNCATED AT 250 WORDS)
采用定量受体放射自显影方法，对人脑胶质瘤手术标本（6例良性星形细胞瘤和7例多形性胶质母细胞瘤）及正常人类皮质中的内皮素受体进行定位和特性研究。在人类额叶皮质灰质中检测到少量的[125I]内皮素-1（[125I]ET-1）结合位点，白质中结合较少。相反，在星形细胞瘤组织切片中均匀存在相对较高数量的[125I]ET-1结合位点，而在多形性胶质母细胞瘤中，较高数量的[125I]ET-1结合位点异质性地位于具有假栅栏状外观的细胞群和多形性星形胶质细胞上。来自胶质母细胞瘤的组织切片中的坏死区域没有结合。[125I]ET-1与胶质瘤和正常灰质的结合是特异性的。未标记的ET-1及其天然类似物（ET-2和ET-3）以浓度依赖性方式并以相似的高效能抑制[125I]ET-1与这些病变的结合。可能相关的物质，如离子通道调节剂（ω-芋螺毒素、蜂毒明肽和河豚毒素）、钙通道阻滞剂（尼卡地平）和生长因子（表皮生长因子和胰岛素样生长因子I），不影响与来自胶质瘤或正常额叶皮质的组织切片的结合。Scatchard分析显示，正常皮质和胶质瘤中存在单一类型的内皮素高亲和力结合位点。结合亲和力没有显著差异：6例星形细胞瘤的解离常数（Kd）为2.1±0.5 nM，7例胶质母细胞瘤为2.5±0.4 nM，两个正常皮质分别为1.4 nM和1.5 nM。（摘要截断于250字）
