Characteristics of thermoregulatory and febrile responses in mice deficient in prostaglandin EP1 and EP3 receptors.
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 microg 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 microg kg(-1) increased Tc about 1 degrees C, peaking 2 h after injection. At 100 microg 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 microg kg(-1) LPS, only the initial (< 40 min) increase in Tc was lacking; with 100 microg 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.
Oka
Takakazu
T
Department of Neurology, Beth Israel Deaconess Medical Center and Program in Neuroscience and Harvard Medical School, Boston, MA 02115, USA.
Oka
Kae
K
Kobayashi
Takuya
T
Sugimoto
Yukihiko
Y
Ichikawa
Atsushi
A
Ushikubi
Fumitaka
F
Narumiya
Shuh
S
Saper
Clifford B
CB
D000818:Animals; D001833:Body Temperature Regulation / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000503:physiopathology*; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007509:Irritants / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018078:Receptors, Prostaglandin E / Q000235:genetics* / Q000378:metabolism*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D012919:Social Behavior; D013315:Stress, Psychological / Q000503:physiopathology; D014425:Turpentine / Q000494:pharmacology
D007509:Irritants; D008070:Lipopolysaccharides; C545636:Ptger1 protein, mouse; C545648:Ptger3 protein, mouse; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D014425:Turpentine