Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study investigated the involvement of endogenous melatonin in the prevention of pancreatic damage provoked by caerulein-induced pancreatitis (CIP) by using the luzindole, the antagonist of melatonin MT2 receptors. CIP was produced by subcutaneous infusion of caerulein to conscious rats (25 microg/kg). Luzindole (1, 2 or 4 mg/kg) was given as an intraperitoneal bolus injection 30 min prior to the start of CIP. Lipid peroxidation products, malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) were measured in the pancreas by LPO-584 commercial kit. CIP was confirmed by histological examination and manifested by significant increases of plasma activities of amylase, lipase and tumor necrosis factor alpha (TNFalpha) (by 500%, 1000% and 600%, respectively) comparing to the control values. This was accompanied by a 40% limitation in pancreatic blood flow (PBF) and by 200% increase of MDA+4-HNE in the pancreas of CIP rats. Administration of luzindole to the CIP rats reduced PBF, aggravated the histological manifestations of pancreatitis, resulted in the significant augmentation of pancreatic MDA + 4-HNE content, and produced the marked increases of plasma levels of lipase, amylase and TNFalpha, comparing to the values observes in the rats with CIP alone. These results suggest that endogenous melatonin through its receptor MT2 plays an important role in the attenuation of pancreatic damage produced by overstimulation with caerulein.
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PMID:Role of endogenous melatonin and its MT2 receptor in the modulation of caerulein-induced pancreatitis in the rat. 1251 Aug 64

Melatonin was thought to originate primarily from the pineal gland and to be secreted during the night, but recent studies revealed that gastrointestinal (GI) tract presents another, many times larger, source of melatonin that contributes significantly to the circulating concentration of this indole. Melatonin may exert a direct effect on GI tissues but its major influence on GI organs seems to occur indirectly, via the brain-gut axis including peripheral receptors, sensory afferent (vagal or sympathetic) pathways and central nervous system (CNS) acting on these organs via autonomic efferents and neuromediators. This article reviews and updates our experience with the fascinating molecule, as related to GI organs, with special focus on secretory activity of the stomach and pancreas and the maintenance of their tissue integrity. In addition to being released into the circulation, melatonin is also discharged into the gut lumen and this appears to be implicated in the postprandial stimulation of pancreatic enzyme secretion, mediated by melatonin-induced release of cholecystokinin, acting through entero-gastro-pancreatic reflexes. Although exerting certain differences in the mechanism of action on gastric and pancreatic secretory activities, melatonin derived from its precursor L-tryptophan, exhibits similar highly protective actions against the damage of both the stomach and the pancreas and accelerates the healing of chronic gastric ulcerations by stimulating the microcirculation and cooperating with arachidonate metabolites such as prostaglandins, with nitric oxide released from vascular endothelium, and/or sensory nerves and with their neuropeptides such as calcitonin gene related peptide. The beneficial effects of melatonin results in gastro- and pancreato-protection, prevents various forms of gastritis and pancreatitis through the activation of specific MT2-receptors and scavenges reactive oxygen species (ROS). Melatonin counteracts the increase in the ROS-induced lipid peroxidation and preserves, at least in part, the activity of key anti-oxidizing enzymes such as superoxide dismutase. It is proposed that melatonin should be considered as the agent exerting an important role in prevention of gastric and pancreatic damage and in accelerating healing of gastric ulcers.
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PMID:Melatonin as an organoprotector in the stomach and the pancreas. 1568 61

In chronic pancreatitis and pancreatic cancer, progressive fibrosis with the accumulation of extracellular matrix occurs. The main extracellular matrix-producing cell types are retinoid-storing pancreatic stellate cells (PSCs) of mesenchymal origin. Similar to liver stellate cells, quiescent PSCs undergo activation and acquire a myofibroblast-like phenotype in response to pro-fibrogenic mediators (reactive oxygen species, cytokines and toxic metabolites). Activated PSCs differ in their differentiation stage and are characterized by the expression of glial fibrillary-acidic protein, alpha-smooth muscle actin, and nestin. As G-protein-coupled receptors were described to regulate PSC differentiation, we investigated tissue samples from patients with pancreatitis and ductal pancreatic adenocarcinoma for the expression of G-protein-coupled melatonin receptors MT1 and MT2 by double immunofluorescence staining. We show that MT1, but not MT2, is occasionally expressed in PSCs in normal tissue, while in the diseased tissue MT1 is found at high rates in activated PSCs at all stages, and, additionally, in ductal epithelial cells. It is speculated that MT1 activation by its ligand melatonin regulates proliferation and differentiation of PSCs. Prevention of myofibroblast formation by MT1 activation could explain favourable effects of the pineal hormone melatonin on the outcome of pancreatic fibrosis in animal models.
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PMID:Pancreatic stellate/myofibroblast cells express G-protein-coupled melatonin receptor 1. 1899 76

The authors present results of the investigation of melatonin receptors expression in lymphocytes in dynamics in 102 patients with acute pancreatitis of mild and severe form and in 50 volunteers. A correlated analysis was made between obtained results of laboratory and instrumental researches and clinical course of acute pancreatitis. The decrease of MT1 receptors expression was noted on 25% in patients with acute pancreatitis. The decline of MT2 receptors expression was observed on 40% of patients with acute severe pancreatitis and in a case of acute mild pancreatitis--on 15.5%, respectively. Values of MT1 and MT2 expression were equal between healthy volunteers. The decline of MT2 expression was a prognostic unfavourable sign. Obtained results of dynamic expression assessment of MT-receptors were presented as MT2/MT1 indices. Given index didn't change during disease, because of this, the index could be used as a prognostic development marker of destructive form of acute pancreatitis at the moment of patient's admission to hospital. Mean values of MT2/MT1 were determined for the purpose of universalization of used method (1.13 +/- 0.09 for mild form and 0.81 +/- 0.09 for severe form of acute pancreatitis, respectively).
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PMID:[Results of dynamic assessment of melatonin receptor expression in lymphocytes in patients with acute mild and severe pancreatitis]. 2505 9