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Vol. 11, No. 1, 2002
Issue release date: 2002

Prostanoid Signal Integration and Cross Talk

Wise H. · Wong Y.H. · Jones R.L.
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Abstract

The enzymatic machinery for the production of prostanoids and the receptors responsible for detecting their presence are widely distributed in the body. One pair of prostanoids, prostacyclin and thromboxane A2, are particularly important in the control of haemodynamics and haemostasis. Prostacyclin achieves its antiplatelet effect by acting as a physiological antagonist, but displays some selectivity towards thromboxane A2-mediated platelet activation, possibly by virtue of the inability of thromboxane A2 receptors to couple directly to Gi proteins, and because platelet-derived endoperoxides can act as substrates for prostacyclin synthesis in endothelial cells. At low concentrations, prostaglandin E2 can synergize with thromboxane A2 by acting on the EP3 subtype of prostaglandin E2 receptor, resulting in opposition to the protective function of prostacyclin. In contrast, high concentrations of prostaglandin E2 act on the prostacyclin receptor, and possibly the prostaglandin D2 receptor, to turn off platelet activation. Integration of prostanoid signalling in the vascular system is similarly complex, and interpretation of data is further complicated by the regional distribution of prostanoid receptors in different vascular beds, and the poor selectivity of agonists and antagonists.



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