Qadri Fatimunnisa, Rimmele Florian, Mallis Lisa, Häuser Walter, Dendorfer Andreas, Jöhren Olaf, Dominiak Peter, Leeb-Lundberg L M Fredrik, Bader Michael
Biol Chem. 2016 Jan 1;397(2):97-109. doi: 10.1515/hsz-2015-0206.
Bradykinin (BK) and des-Arg9-BK are pro-inflammatory mediators acting via B2 (B2R) and B1 (B1R) receptors, respectively. We investigated the role of B2R and B1R in lipopolysaccharide (LPS)-induced hypothalamo-pituitary-adrenal (HPA) axis activation in SD rats. LPS given intraperitoneally (ip) up-regulated B1R mRNA in the hypothalamus, both B1R and B2R were up-regulated in pituitary and adrenal glands. Receptor localization was performed using immunofluorescence staining. B1R was localized in the endothelial cells, nucleus supraopticus (SON), adenohypophysis and adrenal cortex. B2R was localized nucleus paraventricularis (PVN) and SON, pituitary and adrenal medulla. Blockade of B1R prior to LPS further increased ACTH release and blockade of B1R 1 h after LPS decreased its release. In addition, we evaluated if blockade of central kinin receptors influence the LPS-induced stimulation of hypothalamic neurons. Blockade of both B1R and B2R reduced the LPS-induced c-Fos immunoreactivity in the hypothalamus. Our data demonstrate that a single injection of LPS induced a differential expression pattern of kinin B1R and B2R in the HPA axis. The tissue specific cellular localization of these receptors indicates that they may play a crucial role in the maintenance of body homeostasis during endotoxemia.
缓激肽（BK）和去-Arg9-BK分别是通过B2受体（B2R）和B1受体（B1R）发挥作用的促炎介质。我们研究了B2R和B1R在脂多糖（LPS）诱导的SD大鼠下丘脑-垂体-肾上腺（HPA）轴激活中的作用。腹腔注射（ip）LPS可使下丘脑B1R mRNA上调，垂体和肾上腺中B1R和B2R均上调。采用免疫荧光染色进行受体定位。B1R定位于内皮细胞、视上核（SON）、腺垂体和肾上腺皮质。B2R定位于室旁核（PVN）和SON、垂体和肾上腺髓质。LPS注射前阻断B1R可进一步增加促肾上腺皮质激素（ACTH）释放，LPS注射1小时后阻断B1R则降低其释放。此外，我们评估了中枢激肽受体阻断是否影响LPS诱导的下丘脑神经元刺激。同时阻断B1R和B2R可降低LPS诱导的下丘脑c-Fos免疫反应性。我们的数据表明，单次注射LPS可诱导HPA轴中激肽B1R和B2R的差异表达模式。这些受体在组织中的特异性细胞定位表明，它们可能在内毒素血症期间维持机体稳态中发挥关键作用。
