Peters H D, Dinnendahl V, Schönhöfer P S
Naunyn Schmiedebergs Arch Pharmacol. 1975;289(1):29-40. doi: 10.1007/BF00498027.
The effect non-steroidal anti-inflammatory drugs on formation and release of glycosaminoglycans (GAG) and cyclic 3',5'-AMP levels was studied in embryonic mouse fibroblasts. The results were compared and correlated with the action of these drugs on cyclic 3',5'-AMP-dependent as well as independent protein kinase obtained from bovine diaphragm. 1. Phenylbutazone dose-dependently decreased cyclic 3',5'-AMP levels and GAG secretion both in unstimulated and PGE1 stimulated cells. 2. Indometacin decreased cyclic 3',5'-AMP levels and GAG secretion only in cells with elevated cyclic 3',5'-AMP levels after stimulation by PGE1. 3. Sodium salicylate decreased cyclic 3',5'-AMP levels in the presence and absence of PGE1. However, GAG secretion was reduced only in cells with elevated cyclic 3',5'-AMP levels, since the drug activated cyclic 3',5'-AMP-independent protein kinase activity, thus presumably precluding changes in GAG formation at low levels of cyclic 3',5'-AMP. 4. Mefenamic acid decreased cyclic 3',5'-AMP levels in cells stimulated by PGE1, whereas GAG secretion was increased both in the absence and presence of PGE1. This increase in GAG secretion was closely correlated to an enhanced cyclic 3',5'-AMP-dependent and independent protein kinase activity. The results indicate that non-steroidal anti-inflammatory drugs may exert their effects on GAG formation by interfering with cyclic 3',-5'-AMP formation or function.
在胚胎小鼠成纤维细胞中研究了非甾体抗炎药对糖胺聚糖（GAG）形成与释放以及环磷酸腺苷（cAMP）水平的影响。将这些结果与这些药物对从牛膈肌中获得的cAMP依赖性及非依赖性蛋白激酶的作用进行了比较和关联。1. 保泰松在未刺激和前列腺素E1（PGE1）刺激的细胞中均剂量依赖性地降低cAMP水平和GAG分泌。2. 吲哚美辛仅在PGE1刺激后cAMP水平升高的细胞中降低cAMP水平和GAG分泌。3. 水杨酸钠在有和没有PGE1存在的情况下均降低cAMP水平。然而，GAG分泌仅在cAMP水平升高的细胞中减少，因为该药物激活了cAMP非依赖性蛋白激酶活性，因此可能在低水平cAMP时阻止GAG形成的变化。4. 甲芬那酸在PGE1刺激的细胞中降低cAMP水平，而在有和没有PGE1存在的情况下GAG分泌均增加。GAG分泌的这种增加与增强的cAMP依赖性及非依赖性蛋白激酶活性密切相关。结果表明，非甾体抗炎药可能通过干扰cAMP的形成或功能对GAG形成发挥作用。
