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Mechanism of Inhibitory Action of Cyclooxygenase-2 Inhibitors in Human Platelets



S.A. Saeed , H. Rasheed , T.M. Ali , Y. Qazi , S. Kabraji , L. Paul , R. Khan , F.A. Hussain and S. Ahmad
 
ABSTRACT

This study was conducted to investigate the effects of nimesulide in platelet aggregation. It shows that nimesulide (1-100 μ M) inhibited platelets aggregation induced by adrenaline, (20-200 μ M). It also inhibed thromboxane A2 (TXA2) formation by platelets at low concentration (IC50; 1 μ M). However, much lower concentrations of nimesulide (0.01-0.1 μ M) potentiated the aggregatory response of subthreshold concentrations of adrenaline (0.2-2 μ M). Such an effect was blocked by Ca2+-channel blockers, verapamil and diltiazem (IC50: 7 and 46 μ M, respectively), nitric oxide donor, SNAP (IC50: 2 μ M) and cinchonine (10 nM) but not by genistein (up to 10 μ M). These results are indicative of the concentration-dependent dual effects of nimesulide on human platelet aggregation. The synergistic effect of low doses of nimesulide and adrenaline seems to be mediated through inhibition of multiple signaling pathways.

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  How to cite this article:

S.A. Saeed , H. Rasheed , T.M. Ali , Y. Qazi , S. Kabraji , L. Paul , R. Khan , F.A. Hussain and S. Ahmad , 2004. Mechanism of Inhibitory Action of Cyclooxygenase-2 Inhibitors in Human Platelets. Journal of Biological Sciences, 4: 515-520.

DOI: 10.3923/jbs.2004.515.520

URL: https://scialert.net/abstract/?doi=jbs.2004.515.520

REFERENCES
Baldassarre, D., N. Mores, S. Colli, F. Pazzucconi, C.R. Sirtori and E. Tremoli, 1997. Platelet alpha 2-adrenergic receptors in hypercholesterolemia: Relationship between binding studies and epinephrine-induced platelet aggregation. Clin. Pharmacol. Ther., 61: 684-691.
PubMed  |  

Bevilacqua, M., T. Vago, G. Baldi, E. Renesto, F. Dallegri and G. Norbiato, 1994. Nimesulide decreases superoxide production by inhibiting phosphodiesterase type IV. Eur. J. Pharmacol., 268: 415-423.

Brass, L.F., J.A. Hoxie and D.R. Manning, 1993. Signaling through G proteins and G protein-coupled receptors during platelet activation. Thromb. Haemost., 70: 217-223.
PubMed  |  

Capecchi, P.L., L. Ceccatelli, U. Beermann, F. Laghi-Pasini and T. Di-Perri, 1993. Inhibition of neutrophil function in vitro by nimesulide. Preliminary evidence of an adenosine-mediated mechanism. Arzneimittelforschung, 43: 992-996.

Casolaro, V., S. Meliota, O. Marino, V. Patella, A. de-Paulis, G. Guidi and G. Marone, 1993. Nimesulide, a sulfonanilide nonsteroidal anti-inflammatory drug, inhibits mediator release from human basophils and mast cells. J. Pharmacol. Exp. Ther., 267: 1375-1385.
PubMed  |  

Diodati, J.G., R.O. Cannon, S.E. Epstein and A.A. Quyyumi, 1992. Platelet hyperaggregability across the coronary bed in response to rapid atrial pacing in patients with stable coronary artery disease. Circulation, 86: 1186-1193.
Direct Link  |  

Frolich, J.C., 1997. A classification of NSAIDs according to the relative inhibition of cyclooxygenase isoenzymes. Trends. Pharmacol. Sci., 18: 30-34.

Heemskerk, J.W.M. and O. Sage, 1994. Calcium signaling in platelets and other cells. Platelets, 5: 295-316.
PubMed  |  

James-Kracke, M.R., R.B. Sexe and S.D. Shukla, 1994. Picomolar platelet-activating factor mobilizes Ca to change platelet shape without activating phospholipase C or protein kinase C: Simultaneous fluorometric measurement of intracellular free Ca concentration and aggregation. J. Pharmacol. Exp. Ther., 271: 824-831.

Kimura, Y. and H. Okuda, 1994. Effects of alpha- and beta-adrenergic antagonist on epinephrine-induced aggregation and intracellular free calcium concentration in human platelets. Biochem. Biophys. Res. Commun., 202: 1069-1075.

Mullaney, I., B.H. Shah, A. Wise and G. Milligan, 1995. Expression of the human beta 2-adrenoceptor in NCB20 cells results in agonist activation of adenylyl cyclase and agonist-mediated selective down-regulation of Gs alpha. J. Neurochem., 65: 545-553.

Nieuwland, R., O.L. Wijburg, G. van Willigen and J.W. Akkerman, 1994. α2A-adrenergic receptors activate protein kinase C in human platelets via a pertussis toxin-sensitive G-protein. FEBS Lett., 339: 79-83.
CrossRef  |  

Riendeau, D., M.D. Percival, S. Boyce, C. Brideau and S. Charleson et al., 1997. Biochemical and pharmacological profile of a tetrasubstituted furanone as a highly selective COX-2 inhibitor. Br. J. Pharmacol., 121: 105-117.

Saeed, S.A. and B.H. Shah, 1997. Diversity of agonist-mediated transduction pathways in human platelets. Adv. Exp. Med. Biol., 407: 531-535.
PubMed  |  

Saeed, S.A., A.H. Gilani, R.U. Majoo and B.H. Shah, 1997. Anti-thrombotic and anti-inflammatory activities of protopine. Pharmacol. Res., 36: 1-7.
CrossRef  |  PubMed  |  Direct Link  |  

Shah, B.H. and G. Milligan, 1994. The gonadotrophin-releasing hormone receptor of alpha T3-1 pituitary cells regulates cellular levels of both of the phosphoinositidase C-linked G proteins, Gq alpha and G11 alpha, equally. Mol. Pharmacol., 46: 1-7.

Shah, B.H. and S.A. Saeed, 1995. Phosphatidylinositol 3-kinase inhibitor, wortmannin, inhibits 5-hydroxytryptamine-mediated potentiation of platelet aggregation induced by epinephrine. Res. Commun. Mol. Pathol. Pharmacol., 89: 157-164.

Shah, B.H., B. Safdar, S.S. Virani, Z. Nawaz, S.A. Saeed and A.H. Gilani, 1997. The antiplatelet aggregatory activity of Acacia nilotica is due to blockade of calcium influx through membrane calcium channels. Gen. Pharmacol., 29: 251-255.
CrossRef  |  PubMed  |  Direct Link  |  

Shah, B.H., D.J. MacEwan and G. Milligan, 1995. Gonadotrophin-releasing Hormone receptor agonist-mediated down-regulation of Gq Alpha/G11 Alpha (Pertussis Toxin-insensitive) G proteins in Alpha T3-1 Gonadotroph cells reflects increased G protein Turnover but not Alterations in mRNA levels. Proc. Nat. Acad. Sci. USA., 92: 1886-1890.

Shah, B.H., G. Shamim, S. Khan and S.A. Saeed, 1996. Protein kinase C inhibitor, chelerythrine, potentiates the adrenaline-mediated aggregation of human platelets through calcium influx. Biochem. Mol. Biol. Int., 38: 1135-1141.
PubMed  |  

Shah, B.H., S.A. Saeed, G. Shamim, Z. Nawaz and A.H. Gilani, 1997. Role of phosphatidylinositol 3-kinase in human platelet aggregation. Biochem. Soc. Trans., 25: 600-600.
CrossRef  |  PubMed  |  Direct Link  |  

Shah, B.H., Z. Nawaz, S.S. Virani, I.Q. Ali, S.A. Saeed and A.H. Gilani, 1998. The inhibitory effect of cinchonine on human platelet aggregation due to blockade of calcium influx. Biochem. Pharmacol., 56: 955-960.
CrossRef  |  PubMed  |  Direct Link  |  

Tool, A.T. and A.J. Verhoeven, 1995. Inhibition of the production of platelet activating factor and of leukotriene B4 in activated neutrophils by nimesulide due to an elevation of intracellular cyclic adenosine monophosphate. Arzneimittelforschung., 45: 1110-1114.
Direct Link  |  

Tool, A.T., F.P. Mul, E.F. Knol, A.J. Verhoeven and D. Roos, 1996. The effect of salmeterol and nimesulide on chemotaxis and synthesis of PAF and LTC4 by human eosinophils. Eur. Respir. J. Suppl., 22: 141-145.

Torti, M., M.F. Crouch and E.G. Lapetina, 1992. Epinephrine induces association of pp60src with Gi alpha in human platelets. Biochem. Biophys. Res. Commun., 186: 440-447.
CrossRef  |  

Wang, X., S. Yanagi, C. Yang, R. Inatome and H. Yamamura, 1997. Tyrosine phosphorylation and Syk activation are involved in thrombin-induced aggregation of epinephrine-potentiated platelets. J. Biochem. Tokyo, 121: 325-330.
PubMed  |  

Young, J.M., S. Panah, C. Satchawatcharaphong and P.S. Cheung, 1996. Human whole blood assays for inhibition of prostaglandin G/H synthases-1 and -2 using A23187 and lipopolysaccharide stimulation of thromboxane B2 production. Inflamm. Res., 45: 246-253.
CrossRef  |  

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