Cantabrana B, Perez Vallina J R, Menéndez L, Hidalgo A
Laboratorio de Farmacología, Dpto. Medicina, Facultad de Medicina, Oviedo, Spain.
Life Sci. 1995;57(14):1333-41. doi: 10.1016/0024-3205(95)02090-6.
The effect of several anti-inflammatory drugs (NSAIDs), the calmodulin inhibitor W-7 and cortisol on vanadate-induced tonic contraction and on calmodulin dependent cAMP-phosphodiesterase activity have been assayed. Indomethacin, diclofenac, phenylbutazone, mefenamic acid, naproxen, tolmetin, piroxicam, aspirin and W-7, but not metimazol, produce dose-dependent relaxation of vanadate-induced tonic contraction on isolated rat uterus. Cortisol relaxes the vanadate contraction up to 45%. None of the drugs assayed inhibit the basal activity of phosphodiesterase with concentrations lower than 1 mM. However, indomethacin, diclofenac, phenylbutazone, mefenamic acid, naproxen, piroxicam, aspirin and W-7 inhibit, in a concentration-dependent way, the calmodulin-stimulated activity of phosphodiesterase. The maximum inhibition achieved with tolmetin (1 mM) and cortisol (1 mM) was 38% and 24%, respectively. Metamizol has no effect on basal or/and stimulated phosphodiesterase. This, as far as we know, is the first description of relationship between NSAIDs and calmodulin-dependent processes and our results suggest that the inhibition of calmodulin with NSAIDs may be directly related to their pKa and liposolubility.
我们检测了几种抗炎药物（非甾体抗炎药）、钙调蛋白抑制剂W-7和皮质醇对钒酸盐诱导的强直性收缩以及对钙调蛋白依赖性环磷酸腺苷磷酸二酯酶活性的影响。吲哚美辛、双氯芬酸、保泰松、甲芬那酸、萘普生、托美丁、吡罗昔康、阿司匹林和W-7，但甲巯咪唑不产生，可使分离的大鼠子宫上钒酸盐诱导的强直性收缩产生剂量依赖性松弛。皮质醇可使钒酸盐收缩松弛高达45%。所检测的药物在浓度低于1 mM时均不抑制磷酸二酯酶的基础活性。然而，吲哚美辛、双氯芬酸、保泰松、甲芬那酸、萘普生、吡罗昔康、阿司匹林和W-7以浓度依赖性方式抑制钙调蛋白刺激的磷酸二酯酶活性。托美丁（1 mM）和皮质醇（1 mM）达到的最大抑制率分别为38%和24%。安乃近对基础或/和刺激的磷酸二酯酶均无影响。据我们所知，这是首次描述非甾体抗炎药与钙调蛋白依赖性过程之间的关系，我们的结果表明，非甾体抗炎药对钙调蛋白的抑制作用可能与其pKa和脂溶性直接相关。
