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Thromboxane A 2 (TXA 2) is generated from prostaglandin H 2 by thromboxane-A synthase in a metabolic reaction which generates approximately equal amounts of 12-hydroxyheptadecatrienoic acid (12-HHT). Aspirin irreversibly inhibits platelet cyclooxygenase 1 preventing the formation of prostaglandin H 2 , and therefore TXA 2 .
Thromboxane synthase inhibitors inhibit the final enzyme (thromboxane synthase) in the synthesis of thromboxane. Ifetroban is a potent and selective thromboxane receptor antagonist. [ 10 ] Dipyridamole antagonizes this receptor too, but has various other mechanisms of antiplatelet activity as well.
The human thromboxane A (TXA) synthase is a 60 kDa cytochrome P450 protein with 533 amino acids and a heme prosthetic group.This enzyme, anchored to the endoplasmic reticulum, is found in platelets, monocytes, and several other cell types.
Thromboxane A2 (TX2) has a positive feedback in platelet activation. It is produced by the oxygenation of arachidonic acid by two enzymes: cycloxygenase and thromboxane A2 synthase. TX2 effects are mediated by G protein-coupled receptors, subtypes TPα and TPβ.
A thromboxane synthase has also been identified. Prostaglandin-F synthase (PGFS) catalyzes the formation of 9α,11β-PGF 2α,β from PGD 2 and PGF 2α from PGH 2 in the presence of NADPH. This enzyme has recently been crystallized in complex with PGD 2 [ 11 ] and bimatoprost [ 12 ] (a synthetic analogue of PGF 2α ).
Prostaglandin receptors or prostanoid receptors represent a sub-class of cell surface membrane receptors that are regarded as the primary receptors for one or more of the classical, naturally occurring prostanoids viz., prostaglandin D2, (i.e. PGD2), PGE2, PGF2alpha, prostacyclin (PGI2), thromboxane A2 (TXA2), and PGH2. [1]
The thromboxane receptor (TP) also known as the prostanoid TP receptor is a protein that in humans is encoded by the TBXA2R gene, The thromboxane receptor is one among the five classes of prostanoid receptors [5] and was the first eicosanoid receptor cloned. [6] The TP receptor derives its name from its preferred endogenous ligand thromboxane A ...
The underlying mechanism for the deleterious effect proposes that endothelial cells lining the microvasculature in the body express COX-2, whose selective inhibition results in levels of prostaglandin I2 (PGI2, prostacyclin) down-regulated relative to thromboxane (since COX-1 in platelets is unaffected).