Prostanoid signal integration and cross talk.
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 A(2), 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 A(2)-mediated platelet activation, possibly by virtue of the inability of thromboxane A(2) receptors to couple directly to G(i) proteins, and because platelet-derived endoperoxides can act as substrates for prostacyclin synthesis in endothelial cells. At low concentrations, prostaglandin E(2) can synergize with thromboxane A(2) by acting on the EP(3) subtype of prostaglandin E(2) receptor, resulting in opposition to the protective function of prostacyclin. In contrast, high concentrations of prostaglandin E(2) act on the prostacyclin receptor, and possibly the prostaglandin D(2) 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.
Wise
H
H
Department of Pharmacology, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, SAR, China. helenwise@cuhk.edu.hk
Wong
Y H
YH
Jones
R L
RL
D001792:Blood Platelets / Q000502:physiology; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology*; D020239:Receptor Cross-Talk / Q000502:physiology*
D011453:Prostaglandins