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

我们研究了用湿狗摇晃（WDS）定义的血脑屏障条例，并获得了以下结果。（1）硝酸氧化物（NO）和阿片类受体是一种非选择性NO合成酶（NOS）抑制剂， Nω-氮-L-精氨酸（L-NA），抑制PQ诱导的WDS，可能是D-NA，它的元素是一种较少的潜力抑制剂，不是这样的。对神经性NOS、7-硝基咪唑（7-NI）的选择性抑制剂，抑制WDS的效果良好。L-Arginine （L-Arg），NO的前cursor，L-NA和7-NI对抑制没有影响，但纳洛酮，阿片类受体的拮抗剂，被抑制。在另一边，我们发现了PQ的行政部门被强烈地诱导了WDS。这个WDS被L-NA深深地压抑了。在Hippocampus中没有生产被PQ所破坏。PQ在没有生产中的损失被L-NA抑制，而这种抑制被L-Arg部分逆转。However，这些变化在PQ-诱导的WDS不出现后出现了，而且消失了。这些发现提出了这样的结论：在PQ诱导的WDS中，NO抑制剂的抑制作用可能通过阿片类受体而不是抑制剂的抑制作用。（2） Vasopressin （V1） receptorsA non-peptide V1 receptor antagonist，OPC-21268， suppressed the PQ-induced WDS。在对比中，肽V1受体拮抗剂， [Deamino-Peny D11 y D1，O-Me-Ty y D12 y D1，Argy D18 y D1]-vasopressin对WDS没有影响。这些建议是，V1接收器可能在PQ诱导的WDS中扮演一个次要的角色。OPC-21268的抑制效应可能是通过另一条比V1受体更好的途径。

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.