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Characteristics of thermoregulatory and febrile responses in mice deficient in prostaglandin EP 1 and EP 3 receptors
Author(s) -
Oka Takakazu,
Oka Kae,
Kobayashi Takuya,
Sugimoto Yukihiko,
Ichikawa Atsushi,
Ushikubi Fumitaka,
Narumiya Shuh,
Saper Clifford B.
Publication year - 2003
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2003.00945.x
Subject(s) - receptor , prostaglandin e2 receptor , prostaglandin , prostaglandin e2 , medicine , thermoregulation , endocrinology , chemistry , agonist
Previous studies have disagreed about whether prostaglandin EP 1 or EP 3 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 EP 1 or the EP 3 receptors and measured changes in core temperature ( T c ) by using telemetry. In WT mice, I.P. injection of LPS at 10 μg kg −1 increased T c about 1 °C, peaking 2 h after injection. At 100 μg kg −1 , LPS increased T c , peaking 5‐8 h after injection. LPS at 1 mg kg −1 decreased T c , reaching a nadir at 5‐8 h after injection. In EP 1 receptor knockout (KO) mice injected with 10 μg kg −1 LPS, only the initial (< 40 min) increase in T c was lacking; with 100 μg kg −1 LPS the mice showed no febrile response. In EP 3 receptor KO mice, LPS decreased T c in a dose‐ and time‐dependent manner. Furthermore, in EP 3 receptor KO mice subcutaneous injection of turpentine did not induce fever. Both EP 1 and EP 3 receptor KO mice showed a normal circadian cycle of T c and brief hyperthermia following psychological stress (cage‐exchange stress and buddy‐removal stress). The present study suggests that both the EP 1 and the EP 3 receptors play a role in fever induced by systemic inflammation but neither EP receptor is involved in the circadian rise in T c or psychological stress‐induced hyperthermia in mice.