title: New satiety hormone nesfatin-1 protects gastric mucosa against stress-induced injury: mechanistic roles of prostaglandins, nitric oxide, sensory nerves and vanilloid receptors.
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 3.5h of water immersion and restraint stress (WRS) were determined. Exogenous nesfatin-1 (5-40μg/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.
authors: Department of Physiology Jagiellonian University Medical College, Cracow, Poland.
authors: Alexandra
authors: A
authors: Szlachcic
authors: Zbigniew
authors: Z
authors: Sliwowski
authors: Gracjana
authors: G
authors: Krzysiek-Maczka
authors: Jolanta
authors: J
authors: Majka
authors: Marcin
authors: M
authors: Surmiak
authors: Robert
authors: R
authors: Pajdo
authors: Danuta
authors: D
authors: Drozdowicz
authors: Stanislaw J
authors: SJ
authors: Konturek
authors: Tomasz
authors: T
authors: Brzozowski
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000293:injuries / Q000294:innervation; D005755:Gastrins / Q000097:blood; D007276:Injections, Intraventricular; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D000080866:Nucleobindins; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012527:Satiation / Q000187:drug effects*; D013312:Stress, Physiological; D050916:TRPV Cation Channels / Q000502:physiology*
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D005755:Gastrins; D009419:Nerve Tissue Proteins; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D011453:Prostaglandins; D050916:TRPV Cation Channels; D009569:Nitric Oxide
keywords: Calcitonin gene-related peptide; Gastric blood flow; Gastroprotection; Nesfatin-1; Nitric oxide; Prostaglandins; Sensory nerves; Stress; Vagal nerves