Thromboxane a2

Prostaglandins (PG) are almost ubiquitously present in the organism and are characterized by a broad pharmacological spectrum of action. They belong to the eicosanoids and act as so-called tissue hormones. PGs are not normally stored in the various organs and cells, but are synthesized and released in response to various stimuli.

Substrates for the biosynthesis of prostaglandins are polyunsaturated C20 fatty acids such as arachidonic acid. The C20 fatty acids and their derivatives are also known as eicosanoids (Greek είκοσι ["eicosi"], twenty ).

Arachidonic acid is largely present in the cells in esterified form in the membrane phospholipids. The concentration of free (cytosolic) arachidonic acid, on the other hand, is very low. Only free arachidonic acid can serve as a substrate for cyclooxygenase or lipoxygenases. Eicosanoid biosynthesis therefore depends primarily on the release of C20 fatty acids from the membrane phospholipids. This occurs, for example, through the activity of the membrane-bound phospholipase A2 or C. The activation of eicosanoid biosynthesis occurs through chemical, physiological, pathophysiological and pharmacological stimuli.

PGs exert their effect via prostaglandin receptors. Prostaglandin receptors belong to the group of G-protein-coupled membrane receptors.

Thromboxane A2, also known as TXA2, which is formed from prostaglandin H2 by thromboxane synthase, mediates its effects via the thromboxane receptor, also a membrane-bound G-protein-coupled receptor.

The half-life of active thromboxane A2 in the body is short at 30 seconds. TXA2 is degraded to the inactive thromboxane B2.

Like PGD2 and PG F2α, TXA2 has a bronchoconstrictive effect. Patients with bronchial asthma are particularly sensitive to these prostaglandin derivatives.

Platelet aggregation: Thromboxane is quantitatively the most important prostaglandin produced in platelets. TXA2 induces and promotes the aggregation of thrombocytes via thromboxane receptors expressed there. Degranulation of the platelets releases vasoactive substances such as ADP and serotonin.

There is a fine balance between the thromboxane synthesized in platelets from arachidonic acid and the vasodilatory and anti-aggregatory PGI2(prostacyclin) formed in the endothelia of the vessel wall. Normal TXA2 biosynthesis is important for the primary repair of endothelial damage by aggregating platelets. Low doses of acetylsalicylic acid (e.g. 75-100 mg) inhibit TXA2 biosynthesis in platelets. This does not inhibit endothelial PGI2 synthesis and function. This selective effect of a cyclooxygenase inhibitor is based on the irreversible inhibition of cyclooxygenase. This can be newly formed in endothelia, but not in thrombocytes. The nucleus-free thrombocytes are not capable of protein synthesis.

Tissue factor (TF), a primary activator of the coagulation cascade, is neither produced by vascular endothelia nor by blood cells such as monocytes under normal conditions. However, thromboxane A2 induces TF gene expression in both monocytes and endothelia and can thus initiate the coagulation cascade.

Smooth muscle: Thromboxane induces smooth muscle contraction in vessels (and airways) via thromboxane receptors and thus vasoconstriction.

Immune system: Activated macrophages and monocytes secrete significant amounts of thromboxane (thromboxane A2) and prostaglandin E2. Neutrophil granulocytes produce rather small amounts of PG E2. Mast cells, on the other hand, produce prostaglandin D2 and no PGE2.

Itching: In the atopic mouse model, the application of a TXA2 receptor antagonist was able to inhibit spontaneous itching; an indication that TXA2 could play a pathogenetic role in the itching of atopic eczema.

Cyclooxygenase inhibitors are widely used in therapy. The reduction of TXA2 formation is the goal of secondary prophylaxis after a myocardial infarction has occurred.

1. Andoh T et al (2016) Thromboxane A2 is Involved in Itch-associated Responses in Mice with Atopic Dermatitis-like Skin Lesions. Acta Derm Venereol 96:899-904.
2. Bode M et al (2014) Regulation of tissue factor gene expression in monocytes and endothelial cells: Thromboxane A2 as a new player.Vascul Pharmacol 62:57-62.
3. Sachinidis A et al (1995) Thromboxane A2 and vascular smooth muscle cell proliferation. Hypertension 26:771-780.
4. Byrne JG et al (1993) Cardiac-derived thromboxane A2. An initiating mediator of reperfusion injury? J Thorac Cardiovasc Surgery 105:689-693.
5. Mehta JL et al (1984) Platelet function and biosynthesis of prostacyclin and thromboxane A2 in whole blood after aspirin administration in human subjects. J Am Coll Cardiol 4:806-811.
6. By Euler US (1935) On the specific antihypertensive substance of human prostate and seminal vesicle secretions. Wien Klin Weekly Report 33: 1182-1183.