Intracarotid low dose bradykinin infusion selectively increases tumor permeability through activation of bradykinin B2 receptors in malignant gliomas
Intracarotid low dose bradykinin infusion selectively increases tumor permeability through activation of bradykinin B2 receptors in malignant gliomas
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DOI：
10.1016/s0006-8993(97)01502-3
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发表时间：
1998-05-04
期刊：
影响因子：
2.9
通讯作者：
Black, KL
中科院分区：
文献类型：
--
作者：
Matsukado, K;Sugita, M;Black, KL
颈动脉内低剂量缓激肽灌注可选择性增加脑肿瘤毛细血管通透性。然而，缓激肽选择性地增加向脑肿瘤而不是正常脑的转运的机制尚未明确定义。因此，本研究试图确定缓激肽增加肿瘤通透性的机制是否特别涉及脑肿瘤组织中的缓激肽B2受体。在渗透性研究中，使用了27只患有RG 2胶质瘤的Wistar大鼠，并使用定量放射自显影法测定了放射性标记[C-14]蔗糖的单向转运Ki。缓激肽（10 μ g kg（-1）min（-1））使蔗糖向肿瘤的转运增加2.1倍（p < 0.001）。缓激肽B_2受体拮抗剂D-Arg，[Hyp（3），Thi（5.8），D-Phe（7）]-缓激肽可显著抑制肿瘤对蔗糖的摄取（p < 0.01），而B_1受体拮抗剂des-Arg（9），[Leu（8）]-缓激肽则无此作用。采用免疫组化方法，用B2受体抗血清AS 424检测B2受体在正常脑和肿瘤组织中的分布。脑内RG 2胶质瘤和脑旁肿瘤（BST）中检测到高水平的B2受体，而在正常脑组织中没有检测到。这些结果表明，缓激肽的透化作用是通过缓激肽B2受体介导的，B2受体在肿瘤组织和正常脑组织中的分布差异可能是对肿瘤组织的选择性作用的原因。(C)1998年Elsevier Science B.V.
Intracarotid low dose bradykinin infusion can selectively increase permeability in brain tumor capillaries. However, the mechanism by which bradykinin selectively increases transport into brain tumors and not normal brain has not been clearly defined. This study therefore sought to determine whether the mechanism by which bradykinin increases tumor permeability specifically involves the bradykinin B2 receptor in brain tumor tissue. In permeability studies, 27 Wistar rats with RG2 gliomas were utilized and a unidirectional transport, Ki, of radiolabeled [C-14] sucrose was determined using quantitative autoradiography. Bradykinin (10 mu g kg(-1) min(-1)) increased the transport of sucrose to tumors 2.1-fold compared to saline infusion alone (p < 0.001). The uptake of sucrose in tumors was significantly inhibited by the bradykinin B2 receptor antagonist, D-Arg, [Hyp(3), Thi(5.8), D-Phe(7)]-bradykinin (p < 0.01), but not by the B1 receptor antagonist, des-Arg(9), [Leu(8)]-bradykinin. The distribution of B2 receptors in normal brain and tumor tissue was examined by immunohistochemistry using the B2 receptor antiserum, AS 424. High levels of B2 receptors were detected in intracerebral RG2 glioma and brain surrounding tumor (BST), but not in normal brain tissue. These results indicate that the permeabilizing effects of bradykinin are mediated through bradykinin B2 receptors, and that differences in distribution of B2 receptors between tumor tissue and normal brain may be responsible for the selective effects on tumor tissue. (C) 1998 Elsevier Science B.V.