Dias Jenny Pena, Gariépy Helaine De Brito, Ongali Brice, Couture Réjean
Department of Molecular and Integrative Physiology, Faculty of Medicine, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, QC H3C 3J7, Canada.
Department of Molecular and Integrative Physiology, Faculty of Medicine, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, QC H3C 3J7, Canada.
Peptides. 2015 Jul;69:118-26. doi: 10.1016/j.peptides.2015.04.022. Epub 2015 May 8.
Kinin B1 receptor (B1R) is virtually absent under physiological condition, yet it is highly expressed in models of diabetes mellitus. This study aims at determining: (1) whether B1R is induced in the brain of insulin-resistant rat through the oxidative stress; (2) the consequence of B1R activation on stereotypic nocifensive behavior; (3) the role of downstream putative mediators in B1R-induced behavioral activity. Sprague-Dawley rats were fed with 10% D-glucose in their drinking water or tap water (controls) for 4 or 12 weeks, combined either with a standard chow diet or a diet enriched with α-lipoic acid (1 g/kg feed) for 4 weeks. The distribution and density of brain B1R binding sites were assessed by autoradiography. Behavioral activity evoked by i.c.v. injection of the B1R agonist Sar-[D-Phe(8)]-des-Arg(9)-BK (10 μg) was measured before and after i.c.v. treatments with selective antagonists (10 μg) for kinin B1 (R-715, SSR240612), tachykinin NK1 (RP-67580) and glutamate NMDA (DL-AP5) receptors or with the inhibitor of NOS (L-NNA). Results showed significant increases of B1R binding sites in various brain areas of glucose-fed rats that could be prevented by the diet containing α-lipoic acid. The B1R agonist elicited head scratching, grooming, sniffing, rearing, digging, licking, face washing, wet dog shake, teeth chattering and biting in glucose-fed rats, which were absent after treatment with α-lipoic acid or antagonists/inhibitors. Data suggest that kinin B1R is upregulated by the oxidative stress in the brain of insulin-resistant rats and its activation causes stereotypic nocifensive behavior through the release of substance P, glutamate and NO.
激肽B1受体（B1R）在生理条件下几乎不存在，但在糖尿病模型中高表达。本研究旨在确定：（1）胰岛素抵抗大鼠脑内的B1R是否通过氧化应激被诱导；（2）B1R激活对刻板防御性 nocifensive行为的影响；（3）下游假定介质在B1R诱导的行为活动中的作用。将Sprague-Dawley大鼠的饮用水中加入10% D-葡萄糖或自来水（对照）喂养4周或12周，并结合标准饲料或富含α-硫辛酸（1 g/kg饲料）的饲料喂养4周。通过放射自显影评估脑B1R结合位点的分布和密度。在脑室内注射选择性拮抗剂（10 μg）分别针对激肽B1（R-715，SSR240612）、速激肽NK1（RP-67580）和谷氨酸NMDA（DL-AP5）受体或一氧化氮合酶抑制剂（L-NNA）前后，测量脑室内注射B1R激动剂Sar-[D-Phe(8)]-des-Arg(9)-BK（10 μg）诱发的行为活动。结果显示，喂食葡萄糖的大鼠各脑区的B1R结合位点显著增加，而含α-硫辛酸的饮食可预防这种增加。B1R激动剂在喂食葡萄糖的大鼠中引发抓头、梳理、嗅闻、站立、挖掘、舔舐、洗脸、湿狗样抖动、牙齿打颤和咬噬等行为，在用α-硫辛酸或拮抗剂/抑制剂处理后这些行为消失。数据表明，激肽B1R在胰岛素抵抗大鼠脑内被氧化应激上调，其激活通过P物质、谷氨酸和一氧化氮的释放导致刻板防御性nocifensive行为。
