Characteristics of bradykinin and TPA increases in the PGE2 levels of human urothelial cells.
Characteristics of bradykinin and TPA increases in the PGE2 levels of human urothelial cells.
复制标题
缓激肽和 TPA 的特性会增加人尿路上皮细胞 PGE2 水平。
DOI：
10.1093/carcin/9.7.1173
复制
发表时间：
1988
期刊：
影响因子：
4.7
通讯作者：
Davis,BB
中科院分区：
文献类型：
--
作者：
Zenser,TV;Thomasson,DL;Davis,BB
前列腺素在膀胱癌的发病机制中起着潜在的关键作用。在原代培养的人尿路上皮细胞中比较缓激肽和TPA对前列腺素(PG)E2水平的影响。PGE2水平的升高与TPA的剂量有关，直到加入TPA后30-60分钟才明显升高，在60-120分钟出现较大幅度的升高。环己酰亚胺抑制刺激作用。在TPA刺激的细胞中加入花生四烯酸使PGE2增加到与花生四烯酸刺激的对照组相似的水平，这一水平不被放线菌亚胺改变。与TPA相比，缓激肽升高的PGE2水平在5min(最早的时间点)达到最大，且不被放线菌酮抑制。由TPA和缓激肽引起的PGE2水平升高需要钙。TPA的过度刺激导致对随后的TPA刺激的脱敏，但不包括缓激肽。TPA和缓激肽联合使用至少对PGE2水平有相加作用。这两种激动剂都增加了[~3H]花生四烯酸的释放，其时间过程类似于它们的PGE2反应。缓激肽和TPA似乎通过单独的磷脂酶途径提高花生四烯酸的可获得性，从而增加PGE2水平。因此，人的尿路上皮细胞对TPA和缓激肽刺激前列腺素表现出相似但不同的特征。
Prostaglandins play a potential key role in the pathogenesis of urinary bladder cancer. Bradykinin and TPA increases in prostaglandin (PG)E2levels were compared in primary cultures of human urothelial cells. Increased PGE2levels were dependent upon the dose of TPA and were not apparent until 30–60 min after addition of TPA, with larger increases occurring between 60 and 120 min. Stimulation was inhibited by cycloheximide. Addition of arachidonic acid to TPAstimulated cells increased PGE2to a level similar to that seen in arachidonic acid-stimulated controls, and this level was not altered by cycloheximide. In contrast to TPA, the bradykininincreased PGE2levels were maximal at 5 min (the earliest time-point assessed) and were not inhibited by cycloheximide. Increases in PGE2levels by both TPA and bradykinin required calcium. Excessive stimulation by TPA resulted in a desensitization to subsequent stimulation by TPA, but not bradykinin. Combination of TPA with bradykinin produced at least an additive effect on PGE2levels. Both agonists increased the release of [3H]arachidonic acid over a timecourse similar to their PGE2response. Bradykinin and TPA appear to increase PGE2levels by enhancing arachidonic acid availability through separate phospholipase pathways. Thus, human urothelial cells exhibit similar, but yet distinct profiles for prostaglandin stimulation by TPA and bradykinin.