CALCIUM AND G-PROTEIN-RELATED SPASMOLYTIC EFFECTS OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS ON RAT UTERUS CONTRACTIONS IN-VITRO

The effects of the nonsteroidal anti-inflammatory drugs (NSAIDs) acety lsalicylic acid, metamizole, phenylbutazone, indometacin, piroxicam, n aproxen, tolmetin, diclofenac, and mefenamic acid on methacholine (10 mu mol/l), prostaglandin F-2 alpha (1 mu mol/l), and KCl (60 mmol/l) i nduced contractions of isolated rat uterus were assayed. All of these cause a concentration-dependent inhibition of methacholine and prostag landin F-2 alpha-induced contractions with the exception of acetylsali cylic acid, metamizole, and naproxen. All except acetylsalicylic acid and metamizole relaxed in a concentration-dependent manner the tonic c ontractions induced by KCl. CaCl2 (0.1-10 mmol/l) totally counteracted the relaxant effects of naproxen and tolmetin, but not those of the o ther NSAIDs. Bay K8644 did not revert the effect of the NSAIDs. Pertus sis toxin (50 mu g/l) did not modify the effect of indometacin, mefena mic acid, and tolmetin, but partially antagonized the effects of diclo fenac and naproxen and increased the effect of phenylbutazone and piro xicam. These results suggest that some of the NSAIDs assayed induce sm ooth muscle relaxation by mechanisms independent of prostaglandin synt hesis inhibition, but related to the inhibition of extracellular calci um influx through mechanisms related or unrelated to pertussis toxin s ensible G proteins.