Platelet thromboxane

Srivastava KC. (1989). Effect of onion and ginger consumption on platelet thromboxane production in humans. Prostaglandins Leukot Essent Fatty Acids. 35(3) 183-5. 

M) and human ISN (8.3 /Oral activity in GPB (20 mg/kg PO) was seen as well. A series of very similar compounds, where the carboxyl group of (51) was replaced by a wide variety of substituents at various positions of the ring, was disclosed in a patent from Otsuka [153]. In agreement with other SAR reports, replacement of the t-butyl groups by methyls enhanced 5-LO inhibition, but decreased oral activity in CPE. 

Higuchi, W., Euse, I., Hattori, A., and Aizawa, Y. (1999) Mutations of the platelet thromboxane A (TXA2) receptor in patients characterized by the absence of TXA2-induced platelet aggregation despite normal TXA2 binding activity. Thromb. Haemost. 82, 1528-1531. 

Drug therapy of acute coronary syndromes including unstable angina and non-Q-wave myocardial infarction includes use of aspirin, heparin and anti-ischaemic drugs and is similar in older patients to other age groups. Activation of platelet thromboxane production in the coronary circulation has been demonstrated in unstable angina. The risk of myocardial infarction or death is reduced by approximately 50% by early aspirin therapy in recommended doses of 160-325 mg per day and continued... 

Janssen PL. Consumption of ginger Zingiber officinale roscoe) does not affect ex vivo platelet thromboxane production in humans. Eur J Clin Nutr 1996 50 772-774. 

Ko FN, Wu TS, Lious MJ, Huang TF, Teng CM. Inhibition of platelet thromboxane formation and phosphoinositides breakdown by osthole from Angelica pubescens. Thromb Haemost 1989 62 996-999. 

Pulcinelli FM, Riondino S, Celestini A, et al. Persistent production of platelet thromboxane A2 in patients chronically treated with aspirin. J Thromb Haemost 2005 3 2784-2789. 

Bydlowski, S.P., D Amico, E.A., and Chamone, D.A. 1991. An aqueous extract of guarana (Paullinia cupana) decreases platelet thromboxane synthesis. Braz. J. Med. Biol. Res. 24, 421-424. 

Q10 Yes, aspirin is used in the secondary prevention of a further stroke. Aspirin inhibits the cyclooxygenase (COX) enzyme responsible for producing thromboxane in platelets. Thromboxane is involved in platelet aggregation, an early step in blood coagulation. A low daily dose of aspirin (75 mg) inhibits thromboxane production, preventing platelet aggregation and blood clotting in arteries. 

D Angelo DD, Eubank JJ, Davis MG, Dom II GW. Mutagenic analysis of platelet thromboxane receptor cysteines. Roles in ligand binding and receptor-effector coupling. JBiol Chem 1996 271 6233-40... 

True TA, Mais DE. Localization of [ IJSAP-N, binding in the human platelet thromboxane Aj/prostaglandin Hj recqrtor by proteolytic cleavage analysis. Eur J Pharmacol 1994 266 51-5... 

M eux PR, Mais DE, Hahidika PV. Interactions of dihydropyridine Cap channel agonists with the human platelet thromboxane Aj/prostaglandin Hj recqstor. Eur J Pharmacol 1991 206 15-21... 

Dorn II GW, Liel N, Trask JL, Mads DE, Assey ME, Halusfaka PV. Increased platelet thromboxane Aj/prostagiandin Hj receptors in patients with acute myocardial infarctioa Circulation 1990 81 212-8... 

Collier A, Tymkewycz P, Armstrong R, Young RJ, Jones RL, Oarice BF. Increased platelet thromboxane receptor sensitivity in diabetic patients with proliferative retinopathy. Diabetologia 1986 29 471-4... 

Jaschondc K, Faul C, Weisenberger H, Kronert K, Schroder H, Renn W. Platelet thromboxane Aj/endoperoxide (TXA2/PGH2) receptors in type I diabetes mellitus. Thromb Haemost 1989 61 535-6... 

Wallenburg HCS, RotanansN. Eidianced reactivity of the platelet thromboxane pathwi in normotensive and hypertensive pregnandes witii insuffideirt fetal growth. Am J Obstet Gynecol 1982 144 523-8... 

BRASS LF, SHALLER CC, BELMONTE EJ (1987) Inositol 1,4,5-triphosphate-induced granule secretion in jdatelets. Evidence that the activation of phospholipase C mediated by platelet thromboxane receptm-s involves a guanine micleotide binding protein-dependent mechanism distinct from that of thrombin. Journal of Clinical Investigation, 79,1269-1275. 

Parent CA, Lagarde M, Venton DL and Le Breton G. (1992). Selective modulation of the human platelet thromboxane A2/prostaglandin H2 receptor by eicosapentaenoic and docoaahexaenoic acids in intact platelets and solubilized platelet membranes. J. Biol. Chem. 267,6541-6446. 

Rao AK, Koike K, Day HJ, Smith XB, Holmsen H. Bleeding disorder assodated albumin-dq>endent partial defidency in platelet thromboxane production. Effect of albumin on aradiidcmate metabolism in platelets. Amo J Clin. Path 1985 83 687-696. 

PG synthesis involves four steps (Figme 2). The first two steps are common to all cells involved in prostaglandin synthesis while the final two steps are cell-specific (14-16). Release of the substrate, arachidonic acid, from membrane phospholipid stores by phospholipase is the initial event in prostaglandin synthesis, and this is followed by formation of the common PG intermediate, PGHj catalyzed by PGH synthase. At this point, rearrangement of PGH to form either stabk (PGD / Ej/ F, ) or unstable (platelet thromboxane - TxA, endothelial prostacyclin - PGy products takes place. The final step, also cell-specific, involves breakdown of the active compounds to irractive metabolites. 

Aspirin s permanent inactivation of the anucleate platelet is also responsible for the cumulative effect seen with repeated daily dosing below 100 mg (25). Daily administration of 30 to 50 mg of aspirin has been shown to lead to complete suppression of platelet thromboxane synthesis in 7 to 10 days (25, 30, 31). This, in turn, leads to inhibition of platelet aggregation and prolongation of the bleeding time, a clinical test often useful in identifying patients with platelet functional defects for further study and characterization (28,32). 

By virtue of its effects on both cyclo-oxygenase isoenzymes, aspirin inhibits platelet thromboxane A2 formation. This effect in the platelet is irreversible and will persist for the lifetime of the platelet (that is up to 10 days), since the platelet cannot synthesize new cyclo-oxygenase. It is of clinical significance that the dose of aspirin necessary to inhibit platelet thromboxane A2 (around 40 mg/day) is much lower than that needed to inactivate the subendothehal prostacychn (PGI2). Hence, platelet aggregation is inhibited, with some associated dilatation of coronary and cerebral arterioles, at doses that do not... 

Hanley SP, Bevan J, Cockbill SR, Heptinstall S. Differential inhibition by low-dose aspirin of human venous prostacyclin synthesis and platelet thromboxane synthesis. Lancet 1981 1(8227) 969-71. 

A report has raised the possibility that patients vvith a known prothrombotic state and raised platelet thromboxane A2 production may be at high risk of thrombosis when selective COX-2 inhibitors are used (4). 

COX-2 inhibitors inhibit the synthesis of prostacyclin in the vascular wall but not platelet thromboxane production. They could therefore theoretically increase the risk of cardiovascular events by shifting the hemostatic balance toward a prothrombotic state. However, it is not clear that theory has much impact on reality. 

PGI2. In vitro stndies have shown that COX-2 expression is up-regulated in endothelial cells by laminar shear stress (73). Furthermore, selective COX-2 inhibitors reduce systemic PGI-2 production in healthy volunteers (74). The clinical implications of these observations are unknown. In theory, COX-2 selective NSAIDs might increase the risk of thromboembolic cardiovascular events because of preferential inhibition of endothehal prostacychn synthesis without corresponding inhibition of platelet thromboxane synthesis, but no rehable data are available on the occurrence of cardiovascnlar events in patients treated with COX-2 selective or non-selective NSAIDs. 

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