Thromboxane

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Thromboxane A2
Thromboxane A2
Thromboxane B2
Thromboxane B2

Thromboxane is a member of the family of lipids known as eicosanoids. The two major thromboxanes are thromboxane A2 and thromboxane B2.

Thromboxane is named for its role in clot formation (thrombosis).

Contents

[edit] Production

Enzymes and substrates associated with thromoboxane and prostacyclin synthesis.
Enzymes and substrates associated with thromoboxane and prostacyclin synthesis.
Eicosanoid synthesis.
Eicosanoid synthesis.

It is produced in platelets by thromboxane-A synthase from the endoperoxides produced by the cyclooxygenase (COX) enzyme from arachidonic acid.

[edit] Mechanism

Thromboxane acts by binding to any of the thromboxane receptors, G-protein coupled receptors coupled to the G protein Gq[1].

[edit] Functions

Thromboxane is a vasoconstrictor and a potent hypertensive agent, and it facilitates platelet aggregation.

It is in homeostatic balance in the circulatory system with prostacyclin, a related compound. The mechanism of secretion of thromboxanes from platelets is still unclear.

[edit] Role of A2 in platelet aggregation

Thromboxane A2 (TXA2), produced by activated platelets, has prothrombotic properties, stimulating activation of new platelets as well as increasing platelet aggregation.

Platelet aggregation is achieved by mediating expression of the glycoprotein complex GP IIb/IIIa in the cell membrane of platelets. Circulating fibrinogen binds these receptors on adjacent platelets, further strengthening the clot.

[edit] Pathology

It is believed that the vasoconstriction caused by thromboxanes plays a role in Prinzmetal's angina.

[edit] Suppression

See also: Mechanism of action of aspirin and Aspirin

The widely used drug aspirin acts by inhibiting the ability of the COX enzyme to synthesize the precursors of thromboxane within platelets. Low-dose, long-term aspirin use irreversibly blocks the formation of thromboxane A2 in platelets, producing an inhibitory effect on platelet aggregation. This anticoagulant property makes aspirin useful for reducing the incidence of heart attacks.[2] 40 mg of aspirin a day is able to inhibit a large proportion of maximum thromboxane A2 release provoked acutely, with the prostaglandin I2 synthesis being little affected; however, higher doses of aspirin are required to attain further inhibition.[3] One side effect of this is that people who regularly take aspirin will suffer from excessive bleeding whenever the skin is perforated.

[edit] References

  1. ^ Rat kidney thromboxane receptor: molecular cloning, signal ...
  2. ^ [1] American Heart Association: Aspirin in Heart Attack and Stroke Prevention "The American Heart Association recommends aspirin use for patients who've had a myocardial infarction (heart attack), unstable angina, ischemic stroke (caused by blood clot) or transient ischemic attacks (TIAs or "little strokes"), if not contraindicated. This recommendation is based on sound evidence from clinical trials showing that aspirin helps prevent the recurrence of such events as heart attack, hospitalization for recurrent angina, second strokes, etc. (secondary prevention). Studies show aspirin also helps prevent these events from occurring in people at high risk (primary prevention)."
  3. ^ Tohgi, H; S Konno, K Tamura, B Kimura and K Kawano (1992). "Effects of low-to-high doses of aspirin on platelet aggregability and metabolites of thromboxane A2 and prostacyclin". Stroke Vol 23: 1400–1403. PMID 1412574. 

[edit] External links

v • d • e
Autacoids, unsaturated fatty acids: Eicosanoids
Prostanoids
Prostaglandins - Thromboxanes (A2, B2)
Leukotrienes
Other
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