Meininger C J, Wu G
Department of Medical Physiology, Texas A&M University, College Station 77843-1114, USA.
J Pharmacol Exp Ther. 1997 Apr;281(1):448-53.
This study was conducted to test the hypothesis that L-glutamine has differential effects on nitric oxide (NO) synthesis from L-arginine in bovine venular endothelial cells (EC) stimulated by A23187 (a Ca++ ionophore) and receptor-mediated vasodilators (bradykinin and substance P). EC were cultured at 37 degrees C for 24 h in the presence of 0.4 mM L-arginine and 0.0 to 2.0 mM L-glutamine with or without 1 microM A23187, 1 microM bradykinin or 10 microM substance P. The release of nitrite and nitrate by EC was used as an indicator of NO synthesis. A23187, bradykinin or substance P increased NO synthesis from L-arginine by EC in the presence or absence of L-glutamine. The addition of L-glutamine (0.5 and 2 mM) markedly increased intracellular concentrations of L-glutamine, L-glutamate and L-aspartate and decreased NO synthesis by EC in a concentration-dependent manner in the presence or absence of A23187, bradykinin or substance P. L-Glutamine had no effect on L-arginine uptake by EC or on intracellular L-arginine concentration. Neither L-glutamine nor its glutaminase metabolites (ammonia, L-glutamate and L-aspartate) had any effect on endothelial NO synthase activity. Taken together, these results suggest that the inhibition by L-glutamine of NO synthesis from L-arginine is unlikely to result from an effect of L-glutamine on L-arginine transport or NO synthase activity. Although the mechanism involved remains unknown, regulation of the arginine-NO pathway by L-glutamine may have pharmacologic and therapeutic implications in such conditions as inflammation and septic shock by inhibiting NO generation from L-arginine in endothelial cells.
L-谷氨酰胺对牛小静脉内皮细胞（EC）中由A23187（一种钙离子载体）以及受体介导的血管舒张剂（缓激肽和P物质）刺激L-精氨酸生成一氧化氮（NO）具有不同影响。将EC在37℃下于含有0.4 mM L-精氨酸和0.0至2.0 mM L-谷氨酰胺的培养基中培养24小时，同时添加或不添加1 μM A23187、1 μM缓激肽或10 μM P物质。EC释放的亚硝酸盐和硝酸盐用作NO合成的指标。无论有无L-谷氨酰胺，A23187、缓激肽或P物质均可增加EC由L-精氨酸生成的NO。添加L-谷氨酰胺（0.5和2 mM）可显著增加细胞内L-谷氨酰胺、L-谷氨酸和L-天冬氨酸的浓度，并在有无A23187、缓激肽或P物质的情况下以浓度依赖方式降低EC的NO合成。L-谷氨酰胺对EC摄取L-精氨酸或细胞内L-精氨酸浓度无影响。L-谷氨酰胺及其谷氨酰胺酶代谢产物（氨、L-谷氨酸和L-天冬氨酸）均对内皮型NO合酶活性无任何影响。综上所述，这些结果表明，L-谷氨酰胺对L-精氨酸生成NO的抑制作用不太可能源于L-谷氨酰胺对L-精氨酸转运或NO合酶活性的影响。尽管其中涉及的机制尚不清楚，但L-谷氨酰胺对精氨酸-NO途径的调节可能通过抑制内皮细胞中L-精氨酸生成NO而在炎症和脓毒性休克等病症中具有药理学和治疗学意义。
