Raben D M, Yasuda K M, Cunningham D D
J Cell Physiol. 1987 Mar;130(3):466-73. doi: 10.1002/jcp.1041300322.
Thrombin and certain prostaglandins are both capable of stimulating the proliferation of cultured cells. Since thrombin stimulates the release and metabolism of arachidonic acid, the precursor of prostaglandins, we examined the relationship between this release and metabolism and the stimulation of cell division in cultured fibroblasts. We also examined the role of prostaglandin synthesis in thrombin-stimulated phosphatidylinositol synthesis. The data in this report demonstrate that the release and metabolism of arachidonic acid are not necessary for thrombin-stimulated cell division. The presence of a low concentration of chymotrypsin prevented thrombin-stimulated arachidonic acid release and metabolism without affecting the stimulation of cell division. Furthermore, thrombin-stimulated cell division occurred in the presence of indomethacin concentrations that prevented cyclooxygenase-mediated metabolism of arachidonic acid. The following experiments showed that thrombin-stimulated phosphatidylinositol synthesis was brought about by a cyclooxygenase-mediated metabolite(s) of arachidonic acid. Indomethacin inhibited the cyclooxygenase-mediated metabolism of arachidonic acid without affecting the thrombin-stimulated release of arachidonic acid. Indomethacin also inhibited thrombin-stimulated phosphatidylinositol synthesis. The dose dependence of this inhibition paralleled the inhibition by indomethacin of cyclooxygenase-mediated metabolism of arachidonic acid. In addition, prostaglandin F2 alpha stimulated phosphatidylinositol synthesis in the presence of indomethacin concentrations which prevented thrombin-stimulated phosphatidylinositol synthesis.
凝血酶和某些前列腺素都能够刺激培养细胞的增殖。由于凝血酶能刺激前列腺素前体花生四烯酸的释放和代谢，我们研究了这种释放和代谢与培养的成纤维细胞中细胞分裂刺激之间的关系。我们还研究了前列腺素合成在凝血酶刺激的磷脂酰肌醇合成中的作用。本报告中的数据表明，花生四烯酸的释放和代谢对于凝血酶刺激的细胞分裂并非必需。低浓度的胰凝乳蛋白酶的存在可阻止凝血酶刺激的花生四烯酸释放和代谢，而不影响细胞分裂的刺激。此外，在吲哚美辛浓度能够阻止花生四烯酸的环氧化酶介导代谢的情况下，仍会发生凝血酶刺激的细胞分裂。以下实验表明，凝血酶刺激的磷脂酰肌醇合成是由花生四烯酸的环氧化酶介导的代谢产物引起的。吲哚美辛抑制花生四烯酸的环氧化酶介导的代谢，而不影响凝血酶刺激的花生四烯酸释放。吲哚美辛还抑制凝血酶刺激的磷脂酰肌醇合成。这种抑制的剂量依赖性与吲哚美辛对花生四烯酸环氧化酶介导代谢的抑制作用平行。此外，在吲哚美辛浓度能够阻止凝血酶刺激的磷脂酰肌醇合成的情况下，前列腺素F2α仍能刺激磷脂酰肌醇合成。
