Theophylline inhibits platelet aggregation, prostaglandin and thromboxane production by a mechanism which is independent of cyclic AMP
- 43 Downloads
Theophylline (0.05–1.0 mM) greatly enhanced the inhibition of platelet aggregation by prostaglandin E1 and at higher concentrations (1.0–4.0 mM) theophylline alone inhibited platelet aggregation, by a mechanism which did not involve significant changes in platelet cAMP levels. These concentrations of theophylline and theophylline in combination with prostaglandin E1, inhibited the synthesis of thromboxane A2, prostaglandin E2 and F2α in stimulated platelets. Theophylline also inhibited arachidonic acid-stimulated platelet aggregation suggesting an effect on cyclooxygenase activity. The calcium ionophore A23187 prevented and reversed the inhibition of platelet aggregation by theophylline, suggesting that theophylline inhibits the rise in intracellular calcium levels which occurs in response to the synthesis of prostaglandin endoperoxides and thromboxane A2.
KeywordsCalcium Prostaglandin Theophylline Platelet Aggregation Intracellular Calcium
Unable to display preview. Download preview PDF.
- M.L. Steer andE.W. Salzman, Cyclic nucleotides in haemostasis and thrombosis. InAdvances in Cyclic Nucleotide Research, vol. 12, pp. 71–92 (Eds.P. Hamet andH. Sands). Raven Press, New York 1980.Google Scholar
- J.M. Gerrard, J.D. Peller, T.P. Krick andJ.G. White,Cyclic AMP and platelet prostaglandin synthesis, Prostaglandins14, 30–51 (1977).Google Scholar
- J.A. Lindgren, H.E. Claesson, H. Kindahl andS. Hammarstrom, Effects of platelet aggregation and adenosine 3′,5′-monophosphate on the synthesis of thromboxane B2 in human platelets. InAdvances in Prostaglandin and Thromboxane Research, vol. 6, pp. 275–281 (Eds.B. Samuelsson, P.W. Ramwell andR. Paoletti). Raven Press, New York 1980.Google Scholar
- G. Ball, G.G. Brereton, M. Fulwood, A.M. Ireland andP. Yates,The effect of prostaglandin E 1 alone and in combination with theophylline or aspirin on collagen induced platelet aggregation on platelet nucleotides including adenosine 3′,5′-cyclic monophosphate, Biochem. J.120, 709–718 (1970).PubMedGoogle Scholar
- G.V.R. Born,Aggregation of blood platelets by adenosine diphosphate and its reversal, Nature, Lond.194, 927–929 (1962).Google Scholar
- W.G. Unger, J.F. Stamford andA. Bennett,Extraction of prostaglandins from human blood, Nature, Lond.233, 336–337 (1971).Google Scholar
- F. Dray, B. Charbonnel andJ. Maclouf,Radioimmunoassay of prostaglandins F, F 1 and E 2 in human plasma, Eur, J. Clin. Invest.5, 311–318 (1975).Google Scholar
- M. Hamberg andB. Samuelsson,Prostaglandin endoperoxides. Novel transformation of arachidonic acid in human platelets, Proc. natn. Acad. Sci. USA71, 3400–3404 (1974).Google Scholar
- V. Stolc,Control of adenyl cyclase by divalent cations and agonists. Analysis of interactions by the Hill equation, Biochim. biophys. Acta596, 267–276 (1979).Google Scholar