New satiety hormone nesfatin-1 protects gastric mucosa against stress-induced injury: Mechanistic roles of prostaglandins,nitric oxide,sensory nerves and vanilloid receptors |
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| Institution: | 1. Department of Psychosomatic Medicine and Psychotherapy, University Hospital Tübingen, Tübingen, Germany;2. Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Germany;3. Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany;1. Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa;2. Department of Rheumatology, Charlotte Maxeke Johannesburg Academic Hospital, Faculty of Health Sciences, University of the Witwatersrand, South Africa;3. Department of Medicine, Division of Critical Care and Pulmonology, Charlotte Maxeke Johannesburg Academic Hospital, Faculty of Health Sciences, University of the Witwatersrand, South Africa;4. Rheumatology Division, Vrije Universiteit Brussel and Universitair Ziekenhuis, Brussel, Belgium;1. Institute of Pharmacy and Pharmacology, School of Pharmaceutical Sciences, University of South China, Hengyang 421001, China;2. Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, China;3. Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Department of Cell Biology and Geneties, University of South China, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, China;1. Charité Center for Internal Medicine and Dermatology, Division for General Internal and Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany;2. Charité Center for Internal Medicine with Gastroenterology and Nephrology, Division for Endocrinology, Diabetes and Nutrition, Charité – Universitätsmedizin Berlin, Berlin, Germany |
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| Abstract: | Nesfatin-1 belongs to a family of anorexigenic peptides, which are responsible for satiety and are identified in the neurons and endocrine cells within the gut. These peptides have been implicated in the control of food intake; however, very little is known concerning its contribution to gastric secretion and gastric mucosal integrity. In this study the effects of nesfatin-1 on gastric secretion and gastric lesions induced in rats by 3.5 h of water immersion and restraint stress (WRS) were determined. Exogenous nesfatin-1 (5–40 μg/kg i.p.) significantly decreased gastric acid secretion and attenuated gastric lesions induced by WRS, and this was accompanied by a significant rise in plasma NUCB2/nefatin-1 levels, the gastric mucosal blood flow (GBF), luminal NO concentration, generation of PGE2 in the gastric mucosa, an overexpression of mRNA for NUBC2 and cNOS, as well as a suppression of iNOS and proinflammatory cytokine IL-1β and TNF-α mRNAs. Nesfatin-1-induced protection was attenuated by suppression of COX-1 and COX-2 activity, the inhibition of NOS with L-NNA, the deactivation of afferent nerves with neurotoxic doses of capsaicin, and the pretreatment with capsazepine to inhibit vanilloid VR1 receptors. This study shows for the first time that nesfatin-1 exerts a potent protective action in the stomach of rats exposed to WRS and these effects depend upon decrease in gastric secretion, hyperemia mediated by COX-PG and NOS-NO systems, the activation of vagal and sensory nerves and vanilloid receptors. |
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| Keywords: | Nesfatin-1 Gastroprotection Stress Gastric blood flow Prostaglandins Nitric oxide Sensory nerves Calcitonin gene-related peptide Vagal nerves |
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