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Spasmolytic and calmodulin inhibitory effect of non-steroidal anti-inflammatory drugs in vitro.

Abstract：

: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.

journal_name

Life Sci

journal_title

Life sciences

authors

Cantabrana B,Perez Vallina JR,Menéndez L,Hidalgo A

doi

10.1016/0024-3205(95)02090-6

subject

Has Abstract

pub_date

1995-01-01 00:00:00

pages

1333-41

issue

14

eissn

0024-3205

issn

1879-0631

pii

0024320595020906

journal_volume

57

pub_type

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