Peripheral naloxone attenuates lipopolysaccharide fever in guinea pigs by an action outside the blood-brain barrier.
Peripheral naloxone attenuates lipopolysaccharide fever in guinea pigs by an action outside the blood-brain barrier.
复制标题
外周纳洛酮通过血脑屏障外的作用减轻豚鼠的脂多糖热。
DOI：
10.1152/ajpregu.1994.266.6.r1824
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Blatteis,CM
中科院分区：
文献类型：
--
作者：
Romanovsky,AA;Shido,O;Ungar,AL;Blatteis,CM
我们以前已经表明，豚鼠对脂多糖（LPS）的发热反应通过皮下注射三级μ受体阿片类药物拮抗剂盐酸纳洛酮（Nal-HCl）而减弱。由于Nal-HCl易于穿过血脑屏障（BBB），因此进行本研究以研究其对发热的影响是外周还是中枢介导的。为此，观察了1）盐酸纳洛酮（23和46 mumol/kg sc），2）四元阿片受体拮抗剂甲基碘化纳洛酮（Nal-mI，46和92 mumol/kg sc）和甲基溴化纳洛酮（Nal-mBr，92 mumol/kg sc）（它们不能穿过血脑屏障）和3）侧脑室注射盐酸纳洛酮（0.25和1.25 mumol）对静脉注射S.在清醒的豚鼠中研究了LPS（2微克/kg）。在无发热条件下，盐酸钠（无论是皮下或icv）及其四元类似物诱导体温过低的反应。外周Nal-HCl、Nal-mI和Nal-mBr也减弱了特征性双相LPS发热的两个阶段。外周阿片类拮抗剂的热效应，三级和四级，与皮肤血管舒张。脑室注射盐酸纳洛酮未引起任何发热减弱。数据的分析表明，盐酸钠具有三种不同的体温调节作用：中枢降温作用，外周治疗作用（这是由于，至少部分地，皮肤血管舒张），和外周解热作用。后一种效应表明，在豚鼠中，循环阿片类药物可能在发热中起作用。
We have previously shown that the febrile response of guinea pigs to lipopolysaccharide (LPS) is attenuated by the subcutaneous administration of the tertiary mu-receptor opioid antagonist naloxone-hydrochloride (Nal-HCl). Because Nal-HCl readily crosses the blood-brain barrier (BBB), this study was undertaken to investigate whether its effect on fever is mediated peripherally or centrally. For this, the effects of 1) Nal-HCl (23 and 46 mumol/kg sc), 2) the quaternary opioid antagonists Nal-methiodide (Nal-mI, 46 and 92 mumol/kg sc) and Nal-methobromide (Nal-mBr, 92 mumol/kg sc), which do not cross the BBB, and 3) intracerebroventricular Nal-HCl (0.25 and 1.25 mumol) on the febrile response to intravenous S. enteritidis LPS (2 micrograms/kg) were investigated in conscious guinea pigs. Under afebrile conditions, both Nal-HCl (whether administered sc or icv) and its quaternary analogues induced hypothermic responses. Peripheral Nal-HCl, Nal-mI, and Nal-mBr also attenuated both phases of the characteristically biphasic LPS fever. The thermal effects of the peripheral opioid antagonists, both tertiary and quaternary, were associated with cutaneous vasodilation. Intracerebroventricularly administered Nal-HCl did not evoke any attenuation of fever. The analysis of the data shows that Nal-HCl possesses three different thermoregulatory actions: a central hypothermic action, a peripheral thermolytic action (which is due to, at least partly, cutaneous vasodilation), and a peripheral antipyretic action. The latter effect suggests that, in guinea pigs, circulating opioids may have a role in fever production.