Characteristics of thermoregulatory and febrile responses in mice deficient in prostaglandin EP1 and EP3 receptors
Characteristics of thermoregulatory and febrile responses in mice deficient in prostaglandin EP1 and EP3 receptors
复制标题
DOI：
10.1113/jphysiol.2003.048140
复制
发表时间：
2003-09-15
影响因子：
5.5
通讯作者：
Saper, CB
中科院分区：
文献类型：
--
作者：
Oka, T;Oka, K;Saper, CB
先前的研究不同意是否前列腺素EP 1或EP 3受体是产生发热反应的关键。因此，我们以不同剂量（1 μ g kg（-1）-1 mg kg（-1））腹腔内（I. P.）野生型（WT）小鼠和缺乏EP 1或EP（3）受体的小鼠，并通过使用遥测技术测量核心温度（T-c）的变化。在野生型小鼠中，腹腔注射10 μ g/kg的LPS使T-c升高约10 ℃，注射后2小时达到峰值。在100 μ g kg（-1）时，LPS增加T-c，在注射后5-8小时达到峰值。1 mg kg（-1）的LPS使T-c降低，在注射后5-8 h达到最低点。在注射10 μ g/kg LPS的EP 1受体敲除（KO）小鼠中，只有初始（< 40分钟）T-c没有增加;注射100 μ g/kg LPS的小鼠没有发热反应。在EP 3受体KO小鼠中，LPS以剂量和时间依赖性方式降低T-c。此外，在EP 3受体KO小鼠中，皮下注射turlitazone不会引起发热。EP 1和EP 3受体敲除小鼠在心理应激（换笼应激和伙伴去除应激）后均表现出正常的T-c昼夜节律周期和短暂的体温过高。本研究表明，EP 1和EP 3受体在全身炎症引起的发热中发挥作用，但EP受体均不参与小鼠T-c或心理应激引起的体温过高的昼夜节律升高。
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 mug kg(-1)-1 mg kg(-1)) intraperitoneally (I.P.) into wild-type (WT) mice and mice lacking the EP1 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 mug kg(-1) increased T-c about 1degreesC, peaking 2 h after injection. At 100 mug 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 EP1 receptor knockout (KO) mice injected with 10 mug kg(-1) LPS, only the initial (< 40 min) increase in T-c was lacking; with 100 mug kg(-1) LPS the mice showed no febrile response. In EP3 receptor KO mice, LPS decreased T-c 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 T-c 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 T-c or psychological stress-induced hyperthermia in mice.