Effect of some cyclooxygenase inhibitors on the increase in guanosine 3':5'-cyclic monophosphate induced by NO-donors in human whole platelets

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Abstract

1. The effect of the NSAIDs indomethacin, indoprofen, diclofenac and acetylsalicylic acid on the increase in guanosine 3':5'-cyclic monophosphate (cyclic GMP) induced by nitric oxide-donor agents was tested in human whole platelets and in platelet crude homogenate. 2. In whole platelets, indomethacin reduced the increase in cyclic GMP induced by the nitric oxide-donors (NO-donors) sodium nitroprusside (NaNP) and S-nitroso-N-acetylpenicillamine (SNAP) in a dose-dependent way, its IC50 being 13.7 μM and 15.8 μM, respectively. 3. Of the other cyclooxygenase inhibitors tested, only indoprofen reduced the increase in cyclic GMP induced by both NO-donors in a dose-dependent way (IC50 = 32.71 μM NaNP and 25.0 μM, SNAP), while acetylsalicylic acid (up to 1000 μM) and diclofenac (up to 100 μM) were ineffective. 4. However, in platelet crude homogenate neither indomethacin nor indoprofen reduced the cyclic GMP production. 5. Indomethacin (10 μM), indoprofen (30 μM), diclofenac (100 μM) and acetylsalicylic acid (1000 μM) showed a comparable efficacy in inhibiting platelet thromboxane B2 (TXB2) production, suggesting that the inhibitory effect of indomethacin and indoprofen on the increase in cyclic GMP induced by both NO-donors was not mediated by inhibition of cyclooxygenase. 6. In vitro, the NSAIDs analysed did not interfere with nitrite production of SNAP. 7. The unhomogeneous behaviour of NSAIDs on the increase in cyclic GMP induced by NO-donors in whole platelets may contribute to the different pharmacological and toxicological characteristics of the drugs, providing new knowledge on the effect of indomethacin and indoprofen.

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Failli, P., Cecchi, E., Tosti-Guerra, C., Mugelli, A., Laffi, G., Zilletti, L., & Giotti, A. (1998). Effect of some cyclooxygenase inhibitors on the increase in guanosine 3’:5’-cyclic monophosphate induced by NO-donors in human whole platelets. British Journal of Pharmacology, 123(7), 1457–1463. https://doi.org/10.1038/sj.bjp.0701745

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