Inoue A, Hashimoto T, Hide I, Nishio H, Nakata Y
Department of Pharmacology, Hiroshima University School of Medicine, Japan.
J Neurochem. 1997 Jan;68(1):128-33. doi: 10.1046/j.1471-4159.1997.68010128.x.
The role of nitric oxide (NO) in the control of 5-hydroxytryptamine (5-HT)-induced release of substance P was investigated in rat spinal cord in vitro. 5-HT facilitated the 60 mM K(+)-evoked release of substance P-like immunoreactive materials (SPLI) from the superfused rat dorsal spinal cord slices without affecting spontaneous SPLI release. The facilitatory effect of 5-HT was significantly inhibited by ICS 205-930 or granisetron (potent and specific 5-HT3 receptor antagonists), by NG-monomethyl-L-arginine (NMMA, a NO synthase inhibitor), and by methylene blue or 1H-[1,2,4] oxadiazolo [4,3-a] quinoxaline-1-one (MB or ODQ, respectively; both are inhibitors of soluble guanylyl cyclase) and was mimicked by 2-methylserotonin (2-m-5-HT, a selective 5-HT3 receptor agonist), L-arginine (a precursor of NO), or 8-bromo-cyclic GMP. NMMA, MB, or ODQ inhibited the 2-m-5-HT-induced increase of cyclic GMP levels in the rat dorsal spinal cord slices. These data suggest that the facilitatory effect of 5-HT on the release of SPLI is mediated by the 5-HT3 receptor and that the intracellular signaling is mediated via NO by an increase in cyclic GMP production.
在体外大鼠脊髓中研究了一氧化氮（NO）在控制5-羟色胺（5-HT）诱导的P物质释放中的作用。5-HT促进了60 mM K⁺诱发的超融合大鼠背侧脊髓切片中P物质样免疫反应性物质（SPLI）的释放，而不影响SPLI的自发释放。5-HT的促进作用被ICS 205-930或格拉司琼（强效且特异性的5-HT3受体拮抗剂）、NG-单甲基-L-精氨酸（NMMA，一种NO合酶抑制剂）以及亚甲蓝或1H-[1,2,4]恶二唑[4,3-a]喹喔啉-1-酮（分别为MB或ODQ；两者均为可溶性鸟苷酸环化酶抑制剂）显著抑制，并被2-甲基5-羟色胺（2-m-5-HT，一种选择性5-HT3受体激动剂）、L-精氨酸（NO的前体）或8-溴环鸟苷酸模拟。NMMA、MB或ODQ抑制了2-m-5-HT诱导的大鼠背侧脊髓切片中环鸟苷酸水平的升高。这些数据表明，5-HT对SPLI释放的促进作用是由5-HT3受体介导的，并且细胞内信号传导是通过NO介导的，通过环鸟苷酸生成的增加来实现。
