Pérez Vallina J R, Cantabrana B, Hidalgo A
Laboratorio de Farmacólogía, Departamento de Medicina, Facultad de Medicina, Oviedo, Spain.
Pharmacology. 1995 May;50(5):324-32. doi: 10.1159/000139298.
The effects of the nonsteroidal anti-inflammatory drugs (NSAIDs) acetylsalicylic acid, metamizole, phenylbutazone, indometacin, piroxicam, naproxen, tolmetin, diclofenac, and mefenamic acid on methacholine (10 mumol/l), prostaglandin F2 alpha (1 mumol/l), and KCl (60 mmol/l) induced contractions of isolated rat uterus were assayed. All of these cause a concentration-dependent inhibition of methacholine and prostaglandin F2 alpha-induced contractions with the exception of acetylsalicylic acid, metamizole, and naproxen. All except acetylsalicylic acid and metamizole relaxed in a concentration-dependent manner the tonic contractions induced by KCl. CaCl2 (0.1-10 mmol/l) totally counteracted the relaxant effects of naproxen and tolmetin, but not those of the other NSAIDs. Bay K8644 did not revert the effect of the NSAIDs. Pertussis toxin (50 micrograms/l) did not modify the effect of indometacin, mefenamic acid, and tolmetin, but partially antagonized the effects of diclofenac and naproxen and increased the effect of phenylbutazone and piroxicam. These results suggest that some of the NSAIDs assayed induce smooth muscle relaxation by mechanisms independent of prostaglandin synthesis inhibition, but related to the inhibition of extracellular calcium influx through mechanisms related or unrelated to pertussis toxin sensible G proteins.
测定了非甾体抗炎药（NSAIDs）乙酰水杨酸、安乃近、保泰松、吲哚美辛、吡罗昔康、萘普生、托美丁、双氯芬酸和甲芬那酸对乙酰甲胆碱（10 μmol/L）、前列腺素F2α（1 μmol/L）和氯化钾（60 mmol/L）诱导的离体大鼠子宫收缩的影响。除乙酰水杨酸、安乃近和萘普生外，所有这些药物均对乙酰甲胆碱和前列腺素F2α诱导的收缩产生浓度依赖性抑制作用。除乙酰水杨酸和安乃近外，所有药物均以浓度依赖性方式松弛氯化钾诱导的强直性收缩。氯化钙（0.1 - 10 mmol/L）完全抵消了萘普生和托美丁的松弛作用，但对其他NSAIDs则无此作用。Bay K8644不能逆转NSAIDs的作用。百日咳毒素（50 μg/L）不能改变吲哚美辛、甲芬那酸和托美丁的作用，但部分拮抗双氯芬酸和萘普生的作用，并增强保泰松和吡罗昔康的作用。这些结果表明，所测定的一些NSAIDs通过独立于前列腺素合成抑制的机制诱导平滑肌松弛，但与通过与百日咳毒素敏感的G蛋白相关或不相关的机制抑制细胞外钙内流有关。
