Overexpression of sigma receptors in nonneural human tumors.
Overexpression of sigma receptors in nonneural human tumors.
复制标题
西格玛受体在非神经人类肿瘤中的过度表达。
作者：
W. Bem;G. Thomas;J. Mamone;S. Homan;B. Levy;F. Johnson;C. Coscia
以前的数据表明，阿片受体发生在神经和非神经人类肿瘤。然而，它最近已被证明，一些假定的阿片类药物结合可能是由于西格玛网站。在这项研究中，评估了非神经人类肿瘤中sigma和阿片受体的存在。肿瘤包括肾癌、结肠癌和肉瘤。[3H]1通过同源竞争结合测定，使用1，3-二-邻甲苯基胍来测定σ受体，当分析时，其提供解离常数和受体密度值。用[3H]-（-）-乙基酮环唑辛（一种与μ、δ和κ亚型相互作用的配体）测量阿片结合。新鲜手术标本从9个人类肿瘤，选择他们的大尺寸，并与非恶性组织进行比较。所有9个肿瘤都含有σ位点，并且解离常数值在27 - 83 nM的范围内。偶尔，两个网站拟合的数据比一个网站的结合更好，这表明存在多个西格玛网站。未检测到阿片样物质结合。通过在肿块周边的几个位置和中心的一个位置取样来评价瘤内变异性。将每个样品平分，保留一部分用于组织学检查，以将形态学特征与受体数据相关联。σ结合的变化与纤维化、活力或坏死的程度无关。受体密度值显示中等的肿瘤内和肿瘤间变异（变异系数分别为8 - 39和27 - 49%）。更重要的是，发现肿瘤中的σ结合大于或等于对照非恶性组织的2倍。
Previous data indicated that opioid receptors occur in both neural and nonneural human tumors. However, it has recently been shown that some of the putative opioid binding may be attributable to sigma sites. In this study the occurrence of sigma and opioid receptors in nonneural human tumors was assessed. The neoplasms included renal and colon carcinomas and a sarcoma. [3H]1,3-di-o-tolylguanidine was used to assay sigma receptors by homologous competition binding assays, which when analyzed provided dissociation constant and receptor density values. Opioid binding was measured with [3H]-(-)-ethylketocyclazocine, a ligand which interacts with mu, delta, and kappa subtypes. Fresh surgical specimens were obtained from 9 human neoplasms, selected for their large size, and compared with nonmalignant tissues. All 9 tumors contained sigma sites, and dissociation constant values were within the range of 27-83 nM. Occasionally, two-site fit the data better than one-site binding, suggesting the presence of multiple sigma sites. Opioid binding was not detected. Intratumoral variability was evaluated by sampling several locations on the periphery of the mass and one in the center. Each of the samples was bisected, with a portion reserved for histological examination to correlate morphological features with receptor data. Changes in sigma binding were not associated with the extent of fibrosis, viability, or necrosis. Receptor density values displayed moderate intra- and intertumoral variation (coefficients of variation, 8-39 and 27-49%, respectively). More important, sigma binding in tumors was found to be greater than or equal to 2-fold higher than that of control nonmalignant tissue.