Lüthy C, Multhaupt M, Oetliker O, Perisic M
Br J Pharmacol. 1983 Aug;79(4):849-54. doi: 10.1111/j.1476-5381.1983.tb10528.x.
Human skin fibroblasts incubated with arachidonic acid in culture show basal release of prostaglandins. They produce the same prostaglandins after stimulation with bradykinin. Basal release of prostaglandins I2 (6-oxo-PGF1 alpha), F2 alpha and E2 is inhibited dose-dependently by both acetylsalicylic acid (ASA) and dipyrone (P less than 0.05). The examined dose-range was 10(-7) to 10(-4) M for both drugs. During the first 5 min after removal of the drugs from the incubation medium, bradykinin-stimulated release remains dose-dependently inhibited (P less than 0.001) in ASA-, but not in dipyrone-treated cultures. The difference between the effects of ASA and of dipyrone is highly significant (P less than 0.0001), whereas the dipyrone-treated cultures are not different from controls. The findings are consistent with cyclo-oxygenase inhibition by ASA as well as by dipyrone. However, the data demonstrate rapid reversibility of the effect of dipyrone. This suggests that in contrast to ASA, dipyrone does not inhibit cyclo-oxygenase by binding covalently to the enzyme.
在培养中用花生四烯酸孵育的人皮肤成纤维细胞显示出前列腺素的基础释放。用缓激肽刺激后,它们产生相同的前列腺素。前列腺素I2(6-氧代-PGF1α)、F2α和E2的基础释放受到乙酰水杨酸(ASA)和安乃近的剂量依赖性抑制(P<0.05)。两种药物的检测剂量范围均为10^(-7)至10^(-4)M。从孵育培养基中去除药物后的最初5分钟内,缓激肽刺激的释放在ASA处理的培养物中仍呈剂量依赖性抑制(P<0.001),而在安乃近处理的培养物中则没有。ASA和安乃近作用之间的差异非常显著(P<0.0001),而安乃近处理的培养物与对照无差异。这些发现与ASA和安乃近对环氧化酶的抑制作用一致。然而,数据表明安乃近的作用具有快速可逆性。这表明与ASA不同,安乃近不是通过与酶共价结合来抑制环氧化酶的。