Open field-induced rise in body temperature and plasma IL-6 is mediated by beta-adrenoceptors in the brain.
Open field-induced rise in body temperature and plasma IL-6 is mediated by beta-adrenoceptors in the brain.
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开放场引起的体温和血浆 IL-6 升高是由大脑中的 β-肾上腺素受体介导的。
DOI：
10.1111/j.1749-6632.1997.tb51726.x
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发表时间：
1997
影响因子：
5.2
通讯作者：
Kluger,MJ
中科院分区：
文献类型：
--
作者：
Soszynski,D;Kozak,W;Rudolph,K;Conn,CA;Kluger,MJ
将大鼠暴露在开阔的场地，一种轻度的心理应激源，会升高体温并增加循环中的白细胞介素-6（IL-6）。[3]然而，人们对心理压力引发这两种反应的途径认识不足。在过去的几年里，研究人员越来越多地将注意力集中在阐明交感神经系统可能参与心理应激诱导的体温和血浆IL-6升高。3，4最近，我们报道了用L-普萘洛尔（一种非选择性β-肾上腺素受体拮抗剂）预处理，防止体温和循环1 L-6.5的旷场升高。在外周（ip）或中枢（icv）注射这种阻断药物后观察到L-普萘洛尔的抑制作用。由于L-普萘洛尔可以通过简单扩散穿过血脑屏障，因此我们假设L-普萘洛尔可以通过竞争中枢神经系统内的P-肾上腺素受体位点来防止应激对体温和细胞因子水平的影响。此外，L-普萘洛尔还具有“局部麻醉”活性。8这就提出了一种可能性，即它的抑制作用可能不仅来自于药物-受体相互作用，而且还来自于药物的“局部麻醉”活性的镇静作用。我们在这项研究中检验的主要假设是血脑屏障内的P-肾上腺素受体负责开放场诱导的体温升高和血浆IL-6活性。为了验证我们的假设，我们使用了纳多洛尔，一种非选择性的β-肾上腺素受体拮抗剂的独特性质。纳多洛尔具有与L-普萘洛尔相同的β-阻断特性，但没有“局部麻醉”活性。此外，由于其低亲脂性，纳多洛尔不能穿透血脑屏障。6
Exposure of rats to an open field, a mild psychological stressor, elevates body temperature and increases circulating interleukin-6 (IL-6).‘3’However, the pathway by which psychological stress triggers both responses is poorly recognized. Over the past few years, investigators increasingly have focused their attention on clarifying the possible involvement of the sympathetic nervous system in the psychological stress-induced rise in body temperature and plasma IL-6.3, 4 Recently, we reported that pretreatment with L-propranolol, a nonselective/3-adrenoceptor antagonist, prevents the open field rise of body temperature and circulating 1L-6.5 The inhibitory effect of L-propranolol was observed after either peripheral (ip) or central (icv) injection of this blocking drug. Since L-propranolol can cross the blood-brain barrier by simple diffusion, 6*’we hypothesize that L-propranolol may prevent the effect of stress on body temperature and cytokine levels by competing for P-adrenoceptor sites inside the central nervous system. In addition, L-propranolol also has “local anesthetic” activity. 8 This raises the possibility that its inhibitory effect may result not only from drug-receptor interactions but also from a tranquilizing effect due to the drug’s “local anesthetic” activity.The major hypothesis we have tested in this study is that P-adrenoceptors inside the blood-brain barrier are responsible for open field-induced elevation of body temperature and plasma IL-6 activity. To test our hypothesis, we used the unique properties of nadolol, a nonselective P-adrenoceptor antagonist. Nadolol has equivalent p-blocking properties to L-propranolol but is devoid of “local anesethetic” a~ tivity.~ Moreover, because of its low lipophilicity, nadolol is unable to penetrate the blood-brain barrier. 6