Characteristics of thermoregulatory and febrile responses in mice deficient in prostaglandin EP1 and EP3 receptors

Takakazu Oka, Kae Oka, Takuya Kobayashi, Yukihiko Sugimoto, Atsushi Ichikawa, Fumitaka Ushikubi, Shuh Narumiya, Clifford B. Saper

Research output: Contribution to journalReview articlepeer-review

150 Citations (Scopus)


Previous studies have disagreed about whether prostaglandin EP1 or EP3 receptors are critical for producing febrile responses. We therefore injected lipopolysaccharide (LPS) at a variety doses (1 μg kg-1-1 mg kg-1) intraperitoneally (I.P.) into wild-type (WT) mice and mice lacking the EP1 or the EP3 receptors and measured changes in core temperature (Tc) by using telemetry. In WT mice, I.P. injection of LPS at 10 μg kg-1 increased Tc. about 1°C, peaking 2 h after injection. At 100 μg kg-1, LPS increased Tc, peaking 5-8 h after injection. LPS at 1 mg kg-1 decreased Tc, reaching a nadir at 5-8 h after injection. In EP1, receptor knockout (KO) mice injected with 10 μg kg-1 LPS, only the initial (< 40 min) increase in Tc was lacking; with 100 μg kg-1 LPS the mice showed no febrile response. In EP3 receptor KO mice, LPS decreased Tc in a dose- and time-dependent manner. Furthermore, in EP3 receptor KO mice subcutaneous injection of turpentine did not induce fever. Both EP1 and EP3 receptor KO mice showed a normal circadian cycle of Tc and brief hyperthermia following psychological stress (cage-exchange stress and buddy-removal stress). The present study suggests that both the EP1 and the EP3 receptors play a role in fever induced by systemic inflammation but neither EP receptor is involved in the circadian rise in Tc or psychological stress-induced hyperthermia in mice.

Original languageEnglish
Pages (from-to)945-954
Number of pages10
JournalJournal of Physiology
Issue number3
Publication statusPublished - Sept 15 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology


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