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Letters to Nature

Nature 388, 678-682 (14 August 1997) | ; Received 28 February 1997; Accepted 4 June 1997

Altered pain perception and inflammatory response in mice lacking prostacyclin receptor

Takahiko Murata1, Fumitaka Ushikubi1, Toshiyuki Matsuoka1, Masakazu Hirata1, Atsushi Yamasaki2, Yukihiko Sugimoto2, Atsushi Ichikawa2, Yoshiya Aze3, Takashi Tanaka4, Nobuaki Yoshida4, Akinori Ueno5, Sachiko Oh-ishi5 & Shuh Narumiya1

  1. Department of Pharmacology, Faculty of Medicine, Sakyo, Kyoto 606-01, Japan
  2. Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Sakyo, Kyoto 606-01, Japan
  3. Fukui Institute for Safety Research, Ono Pharmaceutical Company, Mikuni, Fukui 913, Japan
  4. Division of Molecular and Cellular Immunology, Research Institute Osaka Medical Center for Maternal and Child Health, Izumi, Osaka 590-02, Japan
  5. Department of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Shirokane, Tokyo 108, Japan

Correspondence to: Shuh Narumiya1 Correspondence and requests for materials should be addressed to S.N. (e-mail: Email: snaru@mfour.med.kyoto-u.ac.jp).

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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.