Inoue T, Fukuo K, Morimoto S, Koh E, Ogihara T
Department of Geriatric Medicine, Osaka University Medical School, Japan.
Biochem Biophys Res Commun. 1993 Jul 15;194(1):420-4. doi: 10.1006/bbrc.1993.1836.
We examined the possible participation of nitric oxide (NO) in the activation of cyclooxygenase, a heme-containing enzyme, induced by interleukin-1 (IL-1) in vascular smooth muscle cells (VSMC). IL-1 induced a delayed and prolonged release of both NO and prostaglandin E2 (PGE2) from VSMC. NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthesis, partially but significantly inhibited the PGE2 release induced by IL-1, whereas it completely inhibited the IL-1-induced NO production. The inhibitory effects of L-NMMA on IL-1-induced production of both NO and PGE2 were partially reversed by a 10-fold excess of L-arginine. In addition, coincubation with superoxide dismutase enhanced the IL-1-induced PGE2 release from VSMC. In contrast, 8-bromo-cyclic GMP did not stimulate PGE2 release. Furthermore, 0.2 mM sodium nitroprusside directly stimulated PGE2 release from VSMC. These findings suggest that NO at least in part mediates the IL-1-induced PGE2 production, and that NO may be one of the important signals for the activation of cyclooxygenase to produce PGE2 in VSMC.
我们研究了一氧化氮（NO）在血管平滑肌细胞（VSMC）中白细胞介素-1（IL-1）诱导的含血红素的环氧化酶激活过程中可能发挥的作用。IL-1诱导VSMC延迟并长时间释放NO和前列腺素E2（PGE2）。NO合成抑制剂NG-单甲基-L-精氨酸（L-NMMA）部分但显著抑制IL-1诱导的PGE2释放，而它完全抑制IL-1诱导的NO生成。10倍过量的L-精氨酸可部分逆转L-NMMA对IL-1诱导的NO和PGE2生成的抑制作用。此外，与超氧化物歧化酶共同孵育可增强IL-1诱导的VSMC释放PGE2。相反，8-溴环鸟苷酸不刺激PGE2释放。此外，0.2 mM硝普钠直接刺激VSMC释放PGE2。这些发现表明，NO至少部分介导了IL-1诱导的PGE2生成，并且NO可能是VSMC中环氧化酶激活以产生PGE2的重要信号之一。
