Role of nitric oxide and opioid receptors in the regulation of blood brain barrier permeability

一氧化氮和阿片受体在血脑屏障通透性调节中的作用

• 批准号: 09672335
• 负责人: HARA Shuichi
• 金额: $ 0.77万
• 依托单位: Tokyo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672335/
• 关键词: Paraquat; Nitric oxide; Nω-Nitro-L-arginine; 7-Nitroindazole; Naloxone; Vasopressin; Wet dog shakes; バンプレッシン; オピオイド受容体; バソプレッシン受容体

We studied on the regulation of blood brain barrier by using wet-dog shakes (WDS) induced by paraquat (PQ) in rats, and obtained the following results.(1) Nitric oxide (NO) and opioid receptorsA non-selective NO synthase (NOS) inhibitor, Nω-nitro-L-arginine (L-NA), suppressed the PQ-induced WDS, although D-NA, its enantiomer which was a less potent inhibitor, did not do so. A selective inhibitor to neuronal NOS, 7-nitroindazole (7-NI), suppressed the WDS as well. L-arginine (L-Arg), the precursor of NO, had no effect on the suppression by L-NA and 7-NI, but naloxone, an antagonist of opioid receptors, abolished the suppression. On the other hand, we found that the administration of PQ into the hippocampus strongly induced WDS. This WDS was strongly suppressed by L-NA. NO production in the hippocampus was increased by PQ. The increase in NO production by PQ was suppressed by L-NA, and this suppression was partly reversed by L-Arg. However, these changes in the hippocampal production of NO appeared after the PQ-induced WDS had occurred and disappeared. These findings suggest that NO plays a minor role in the PQ-induced WDS, and the suppressive effect of NOS inhibitors may be mediated through opioid receptors rather than inhibition of the NO production.(2) Vasopressin (V1) receptorsA non-peptide V1 receptor antagonist, OPC-21268, suppressed the PQ-induced WDS. In contrast, a peptide V1 receptor antagonist, [deamino-PenィイD11ィエD1, O-Me-TyィイD12ィエD1, ArgィイD18ィエD1]-vasopressin had no effect on the WDS. These suggest that V1 receptors may play a minor role in the PQ-induced WDS. The suppressive effect of OPC-21268 might be mediated through a pathway other than V1 receptors.

本实验采用百草枯（PQ）诱发大鼠湿狗样震颤（WDS），研究其对血脑屏障的调节作用。(1)一氧化氮（NO）和阿片受体一氧化氮合酶（NOS）的非选择性抑制剂Nω-硝基-L-精氨酸（L-NA）可抑制PQ诱导的大鼠WDS，而其对映体D-NA则无此作用。神经元型NOS选择性抑制剂7-硝基吲唑（7-NI）也能抑制该反应。NO前体L-精氨酸（L-Arg）对L-NA和7-NI的抑制作用无影响，阿片受体拮抗剂纳洛酮可解除这种抑制作用。另一方面，我们发现，PQ到海马的管理强烈诱导WDS。L-NA可强烈抑制该WDS。PQ可增加海马NO的生成。L-NA抑制PQ增加NO产量，L-Arg部分逆转这种抑制作用。然而，海马NO产生的这些变化出现在PQ诱导的WDS发生和消失之后。这些结果表明，NO在PQ诱导的WDS中起次要作用，NOS抑制剂的抑制作用可能是通过阿片受体介导的，而不是抑制NO的产生。(2)非肽类V1受体拮抗剂OPC-21268可抑制PQ诱导的WDS。相反，肽V1受体拮抗剂，[脱氨基-Pen β D11 β D1，O-Me-Ty β D12 β D1，Arg β D18 β D1]-加压素对WDS没有影响。这表明V1受体可能在PQ诱导的WDS中起次要作用。OPC-21268的抑制作用可能通过V1受体以外的途径介导。