Newcombe D S, Fahey J V, Ishikawa Y
Prostaglandins. 1977 Feb;13(2):235-44. doi: 10.1016/0090-6980(77)90005-3.
Human synovial fibroblasts in culture respond to bradykinin with a 20-fold increment in intracellular cyclic AMP concentrations, however bradykinin does not directly activate adenylate cyclase activity in a particulate fraction derived from these cells. Bradykinin evokes a release of labeled arachidonic acid and prostaglandins E and F from synovial fibroblasts pre-labeled with 3H-arachidonic acid. Hydrocortisone inhibits the bradykinin induced increment in cyclic AMP and the release of arachidonic acid and prostaglandins E and F from synovial fibroblasts. Indomethacin, which also inhibits the cyclic AMP response to bradykinin, has no effect on the release of arachidonic acid from synovial fibroblasts. Indomethacin does, however, inhibit the quantity of prostaglandins released into the medium. These studies support the hypothesis that bradykinin does not activate human synovial fibroblast adenylate cyclase, but presumably activates a phospholipase whose products in turn result in the synthesis of prostaglandins. These and other investigations also suggest that a product(s) of the prostaglandin pathway causes the increment in cyclic AMP.
培养的人滑膜成纤维细胞对缓激肽的反应是细胞内环磷酸腺苷(cAMP)浓度增加20倍,然而缓激肽并不会直接激活源自这些细胞的微粒体部分中的腺苷酸环化酶活性。缓激肽会促使预先用³H - 花生四烯酸标记的滑膜成纤维细胞释放标记的花生四烯酸以及前列腺素E和F。氢化可的松会抑制缓激肽诱导的滑膜成纤维细胞中环磷酸腺苷的增加以及花生四烯酸和前列腺素E和F的释放。吲哚美辛同样会抑制对缓激肽的环磷酸腺苷反应,但对滑膜成纤维细胞中花生四烯酸的释放没有影响。不过,吲哚美辛确实会抑制释放到培养基中的前列腺素的量。这些研究支持了这样一种假说,即缓激肽不会激活人滑膜成纤维细胞的腺苷酸环化酶,而是可能激活一种磷脂酶,其产物进而导致前列腺素的合成。这些以及其他研究还表明,前列腺素途径的一种产物会导致环磷酸腺苷增加。