期刊
LIFE SCIENCES
卷 100, 期 2, 页码 85-96出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2014.01.079
关键词
Cyclooxygenase-1; Neuronal nitric oxide synthase; Hypothalamic paraventricular nucleus; Bombesin; S-nitrosylation
资金
- Japan Society for the Promotion of Science [25670354, 23790745, 23790744]
- Smoking Research Foundation in Japan
- Kochi University
- Grants-in-Aid for Scientific Research [25461023, 23790744, 25670354, 26861271, 23790745, 24591013] Funding Source: KAKEN
Aims: Cyclooxygenase (COX) can be activated by nitric oxide-induced (NO-induced) conversion of cysteine thiol group of COX into S-nitrosothiol. We previously reported the involvement of brain COX/NO synthase (NOS) in centrally administered bombesin-, a stress-related neuropeptide, induced secretion of rat adrenal noradrenaline and adrenaline. To examine a possible involvement of the NO-induced modification of COX in bombesin-induced response, we investigated whether bombesin induces close proximity of COX-1 and neuronal NOS (nNOS) or S-nitroso-cysteine in pre-sympathetic spinally projecting neurons in the rat hypothalamic paraventricular nucleus (PVN), a regulatory center of adrenomedullary outflow. Main methods: In twelve-week-old male Wistar rats, pre-sympathetic spinally projecting neurons in the PVN were labeled with a retrograde tracer Fluoro-Gold (FG). After intracerebroventricular administration of bombesin, we performed double immunohistochemical analysis for Fos and COX-1 or nNOS in FG-labeled PVN neurons. We also performed a fluorescent in situ proximity ligation assay (PLA) for visualizing of close proximity (<40 nm) of COX-1 with nNOS or S-nitroso-cysteine. Key. findings: Bombesin significantly increased the number of Fos-immunoreactive cells in FG-labeled PVN neurons with COX-1 or nNOS immunoreactivity. 7-Nitroindazole, a selective nNOS inhibitor, abolished Fos-immunoreactivity induced by bombesin in COX-1-immunoreactive FG-labeled PVN neurons. Bombesin also induced PLA-positive signals indicating close proximity of COX-1/nNOS and COX-1/S-nitroso-cysteine in FG-labeled PVN neurons. Significance: Centrally administered bombesin possibly induces S-nitrosylation of COX-1 through close proximity of COX-1 and nNOS in pre-sympathetic spinally projecting PVN neurons, thereby activating COX-1 during the bombesin-induced activation of central adrenomedullary outflow in the rat. (c) 2014 Elsevier Inc. All rights reserved.
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