ALTERED PAIN PERCEPTION AND INFLAMMATORY RESPONSE IN MICE LACKING PROSTACYCLIN RECEPTOR

Prostanoids are a group of bioactive lipids working as local mediators ' and include D, E, F and I types of prostaglandins (PGs) and thrombox anes. Prostacyclin (PGI(2)) acts on platelets and blood vessels to inh ibit platelet aggregation and to cause vasodilatation, and is thought to be important for vascular homeostasis(2). Aspirin-like drugs, inclu ding indomethacin, which inhibit prostanoid biosynthesis, Suppress fev er, inflammatory swelling and pain, and interfere with female reproduc tion, suggesting that prostanoids are involved in these processes(1,3) , although it is not clear which prostanoid is the endogenous mediator of a particular process, Prostanoids act on seven-transmembrane-domai n receptors which are selective for each type(4). Here we disrupt the gene for the prostacyclin receptor(5) in mice by using homologous reco mbination. The receptor-deficient mice are viable, reproductive and no rmotensive. However, their susceptibility to thrombosis is increased, and their inflammatory and pain responses are reduced to the levels ob served in indomethacin-treated wild-type mice, Our results establish t hat prostacyclin is an antithrombotic agent in vivo and provide eviden ce for its role as a mediator of inflammation and pain.