High Medical School Milutin Milanković, Belgrade, Serbia.
Pharmacol Rep. 2011;63(4):1019-28. doi: 10.1016/s1734-1140(11)70618-1.
Previous results in this laboratory indicate that protamine sulfate (PS) evokes dose-dependent relaxation of both spontaneous and calcium ion-induced uterus activity mediated predominantly by potassium channels and, to a small extent, via β-adrenergic receptors or nitric oxide (NO)-dependent pathways. Indometacin is a nonselective inhibitor of cyclooxygenase (COX 1 and COX 2) that has the ability to delay premature labor by reducing uterine contractions through the inhibition of prostanglandin synthesis in the uterus. This study investigates the effects of indometacin (0.1 and 1 μg/ml) pretreatment on the PS-induced relaxation of isolated uterine smooth muscle. Indometacin pretreatment per se did not change the activity of the uteri. However, indometacin significantly increased PS-induced relaxation of spontaneous uterine contractions. Indometacin pretreatment significantly decreased the magnitude and slope of PS-induced relaxation of calcium ion-induced uterine contractions. Indometacin pretreatment increased CuZnSOD activity and slightly increased GR activity during spontaneous uterine contractions when compared to PS alone. In calcium ion-induced contractions, indometacin pretreatment increased CuZnSOD, GSH-Px and GR activities. These results suggest that, in addition to its COX inhibitory effects, indometacin influences the effects of PS. Therefore, it is possible that indometacin regulates diverse cell functions via its association with lipid membranes by altering micro-environments within the membranes. The above-mentioned processes appear to be partly mediated by redox processes involving ROS, lipid peroxides and antioxidant enzymes. The extent of the PS-mediated effect as different in spontaneous versus calcium ion-induced active uteri.
先前本实验室的研究结果表明，硫酸鱼精蛋白（PS）可诱发自发性和钙离子诱导的子宫活动的剂量依赖性松弛，这种松弛主要通过钾通道介导，而通过β-肾上腺素能受体或一氧化氮（NO）依赖途径的作用较小。吲哚美辛是环氧化酶（COX 1 和 COX 2）的非选择性抑制剂，它通过抑制子宫内前列腺素的合成来延迟早产，从而减少子宫收缩。本研究调查了吲哚美辛（0.1 和 1 μg/ml）预处理对分离的子宫平滑肌中 PS 诱导松弛的影响。吲哚美辛预处理本身并未改变子宫的活性。然而，吲哚美辛显著增加了 PS 诱导的自发性子宫收缩的松弛。吲哚美辛预处理显著降低了 PS 诱导的钙离子诱导的子宫收缩的松弛幅度和斜率。与 PS 单独处理相比，吲哚美辛预处理增加了自发性子宫收缩时 CuZnSOD 的活性，并略微增加了 GR 的活性。在钙离子诱导的收缩中，吲哚美辛预处理增加了 CuZnSOD、GSH-Px 和 GR 的活性。这些结果表明，除了 COX 抑制作用外，吲哚美辛还影响 PS 的作用。因此，吲哚美辛可能通过改变膜内的微环境，通过与脂质膜的结合来调节多种细胞功能。上述过程似乎部分通过涉及 ROS、脂质过氧化物和抗氧化酶的氧化还原过程来介导。在自发性和钙离子诱导的活性子宫中，PS 介导的效应的程度不同。
