Johns R A, Izzo N J, Milner P J, Loeb A L, Peach M J
Department of Anesthesiology, University of Virginia, Charlottesville.
Am J Med Sci. 1988 Apr;295(4):287-92. doi: 10.1097/00000441-198804000-00012.
We have used mixed- and co-cultures of endothelial and vascular smooth muscle cells to investigate the role of phospholipase activation and arachidonic acid metabolites in the production of endothelium-derived relaxing factor (EDRF). Inhibition of phospholipase A2 with para-bromophenacyl bromide, dexamethasone or quinacrine, alone or in combination, blocked arachidonate release by 50%-60% but had no effect on EDRF production as assessed by cyclic GMP accumulation in mixed- or co-cultures of endothelial and vascular smooth muscle cells. Inhibition of the phospholipase C-diacylglycerol (DAG) lipase pathway of arachidonate release by the DAG lipase inhibitor RHC-80267 also caused partial inhibition of arachidonate release and had no effect on EDRF. When both phospholipase A2 and phospholipase C pathways for arachidonate mobilization were inhibited (dexamethasone + RHC 80267), arachidonate release was totally inhibited while EDRF release remained intact. We conclude that neither phospholipase activation nor arachidonate mobilization is required for EDRF release from cultured bovine endothelial cells.
我们利用内皮细胞和血管平滑肌细胞的混合培养及共培养，来研究磷脂酶激活和花生四烯酸代谢产物在内皮衍生舒张因子（EDRF）产生中的作用。用对溴苯甲酰溴、地塞米松或奎纳克林单独或联合抑制磷脂酶A2，可使花生四烯酸释放量减少50%-60%，但在内皮细胞与血管平滑肌细胞的混合培养或共培养中，通过环鸟苷酸积累评估发现，对EDRF的产生没有影响。用二酰基甘油（DAG）脂肪酶抑制剂RHC-80267抑制花生四烯酸释放的磷脂酶C-DAG脂肪酶途径，也会导致花生四烯酸释放部分受抑制，且对EDRF没有影响。当花生四烯酸动员的磷脂酶A2和磷脂酶C途径均被抑制时（地塞米松+RHC 80267），花生四烯酸释放被完全抑制，而EDRF释放仍保持完整。我们得出结论，培养的牛内皮细胞释放EDRF既不需要磷脂酶激活，也不需要花生四烯酸动员。
