Altered pain perception and inflammatory response in mice lacking prostacyclin receptor

Abstract

Prostanoids are a group of bioactive lipids working as local mediators¹ and include D, E, F and I types of prostaglandins (PGs) and thromboxanes. Prostacyclin (PGI₂) acts on platelets and blood vessels to inhibit platelet aggregation and to cause vasodilatation, and is thought to be important for vascular homeostasis². Aspirin-like drugs, including indomethacin, which inhibit prostanoid biosynthesis, suppress fever, inflammatory swelling and pain, and interfere with female reproduction, suggesting that prostanoids are involved in these processes¹,³, although it is not clear which prostanoid is the endogenous mediator of a particular process. Prostanoids act on seven-transmembrane-domain receptors which are selective for each type⁴. Here we disrupt the gene for the prostacyclin receptor⁵ in mice by using homologous recombination. The receptor-deficient mice are viable, reproductive and normotensive. However, their susceptibility to thrombosis is increased, and their inflammatory and pain responses are reduced to the levels observed in indomethacin-treated wild-type mice. Our results establish that prostacyclin is an antithrombotic agent in vivo and provide evidence for its role as a mediator of inflammation and pain.