DefinitionThis section has been translated automatically.
Prostaglandins, PGs, are almost ubiquitously present in the organism and are characterized by a broad pharmacological spectrum of activity. Prostaglandins belong to the eicosanoids and act as so-called tissue hormones. They are normally not stored in the various organs and cells, but are newly synthesized and released in response to various stimuli.
Substrates of the biosynthesis of prostaglandins are polyunsaturated C20 fatty acids like arachidonic acid. The C20 fatty acids and their derivatives are also called eicosanoids (Greek "eicosi" = 20). .
The arachidonic acid is present in the cells mostly in esterified form in the membrane phospholipids. The concentration of free (cytosolic) arachidonic acid is very low. Only free arachidonic acid can serve as a substrate for cyclooxygenase or lipoxygenases. Thus, the eicosanoid biosynthesis primarily depends on the release of the C20 fatty acids from the membrane phospholipids. This is done, for example, by the activity of the membrane-bound phosopholipase A2 or phosopholipase C. The activation of the eicosanoid biosynthesis takes place by chemical, physiological, pathophysiological and pharmacological stimuli.
Prostaglandins have a broad physiological and pathophysiological spectrum of activity. They unfold their effectiveness via prostaglandin receptors. Prostaglandin receptors belong to the group of G-protein coupled membrane receptors.
Thromboxane A2, also called TXA2, which is formed by the thromboxane synthase from prostaglandin-H2, 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 and is 30 seconds. Thromboxane A2 is then degraded to the inactive thromboxane B2.
General informationThis section has been translated automatically.
TXA2 acts like PGD2 and PGF2alpha bronchoconstrictor. Patients with bronchial asthma are particularly sensitive to these prostaglandin derivatives.
Platelet aggregation: Thrombboxane is the quantitatively most important prostaglandin formed in platelets.TXA2 induces and promotes platelet aggregation via thrombboxane receptors expressed in the platelets. Platelet degranulation releases vasoactive substances such as ADP and serotinin.
There is a finely balanced equilibrium between the thrombboxane synthesized from arachidonic acid in platelets and the vasodilatory and antiaggregatory PGI2(prostacyclin) formed in the endothelia of the vessel wall. Normal TXA2 biosynthesis is of great importance for the primary repair of endothelial damage caused by aggregating platelets. Low doses of acetylsalicylic acid (e.g. 75-100mg) inhibit TXA2 biosynthesis in the platelets. This does not inhibit the endothelial PGI2 synthesis and function. This selective inhibition of a cycloxygenase inhibitor is based on the irreversible inhibition of cycloxygenase. This can be produced in endothelia but not in thrombocytes. Nuclear platelets are not capable of protein synthesis.
The tissue factor (TF), a primary activator of the coagulation cascade, is not produced by vascular endothelia or blood cells such as monocytes under normal conditions. Thromboxane A2 (TXA2), however, induces TF gene expression in both monocytes and endothelia and can thus initiate the coagulation cascade.
Smooth muscle: Thromboxane induces via thrombboxane receptors a contraction of smooth muscle at vessels (and airways) and thus vasoconstriction.
Immune system: Activated macrophages and monocytes secrete significant amounts of thrombboxanes (thrombboxane A2) and prostaglandin E2. Neutrophil granulocytes produce rather small amounts of PGE2. 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, suggesting that TXA2 may play a pathogenetic role in the itching of atopic eczema.
Note(s)This section has been translated automatically.
Cyclooxygenase inhibitors are widely used in therapy. The reduction of TXA2 formation is the goal of secondary prophylaxis after a myocardial infarction has occurred.
LiteratureThis section has been translated automatically.
- 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.
- 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.
- Sachinidis A et al (1995) Thromboxane A2 and vascular smooth muscle cell proliferation. Hypertension 26:771-780.
- Byrne JG et al (1993) Cardiac-derived thromboxane A2. An initiating mediator of reperfusion injury? J Thorac Cardiovasc Surgery 105:689-693.
- 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.
- By Euler US (1935) On the specific antihypertensive substance of human prostate and seminal vesicle secretions. Wien Klin Weekly Report 33: 1182-1183.