SPASMOLYTIC AND CALMODULIN INHIBITORY EFFECT OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS IN-VITRO

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 assa yed. Indomethacin, diclofenac, phenylbutazone, mefenamic acid, naproxe n, tolmetin, piroxicam, aspirin and W-7, but not metimazol, produce do se-dependent relaxation of vanadate-induced tonic contraction on isola ted rat uterus. Cortisol relaxes the vanadate contraction up to 45%. N one of the drugs assayed inhibit the basal activity of phosphodiestera se with concentrations lower than 1 mM. However, indomethacin, diclofe nac, phenylbutazone, mefenamic acid, naproxen, piroxicam, aspirin and W-7 inhibit, in a concentration-dependent way, the calmodulin-stimulat ed activity of phosphodiesterase. The maximum inhibition achieved with tolmetin (1 mM) and cortisol (1 mM) was 38% and 24%, respectively. Me tamizol has no effect on basal or/and stimulated phosphodiesterase. Th is, as far as we know, is the first description of relationship betwee n NSAIDs and calmodulin-dependent processes and our results suggest th at the inhibition of calmodulin with NSAIDs may be directly related to their pKa and liposolubility.