Gastric protection by alpha-melanocyte-stimulating hormone against ethanol in rats: involvement of somatostatin.
ABSTRACT The proopiomelanocortin-derived tridecapeptide alpha-melanocyte-stimulating hormone (alpha-MSH) is a neuropeptide that exerts broad anti-inflammatory actions in mammals. This study aimed to investigate the effect of alpha-MSH on ethanol-induced gastric ulcer in rats and to evaluate the involvement of endogenous somatostatin in the actions of the peptide. The rats received 1 mL 75% ethanol or saline orally. alpha-MSH was given (25 micro g/rat; i.p.) alone or following the somatostatin antagonist cyclo-(7-aminoheptanoyl-PH-E-d-Trp-Lys-THR) (10 microM/kg; i.p.) administration. Gastric lesions were scored macroscopically and microscopically following decapitation at 30 min after ethanol challenge. Gastric malondialdehyde (MDA) level, myeloperoxidase (MPO) activity and mast cell counts were assessed. Ethanol-induced gastric hemorrhagic lesions were characterized by increased gastric MDA level, MPO activity and mast cell counts. alpha-MSH treatment decreased the extent of tissue injury and reversed tissue MDA level, MPO activity and mast cell counts. The effect of the peptide on the severity of gastric lesions, MDA level and MPO activity was reversed by the somatostatin antagonist. In conclusion, alpha-MSH is beneficial in a rat model of gastric ulcer via mechanisms which partly involve the endogenous somatostatin.
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ABSTRACT: alpha-Melanocyte-stimulating hormone (alpha-MSH) is a potent inhibitory agent in all major forms of inflammation. To identify a potential mechanism of antiinflammatory action of alpha-MSH, we tested its effects on production of nitric oxide (NO), believed to be a mediator common to all forms of inflammation. We measured NO and alpha-MSH production in RAW 264.7 cultured murine macrophages stimulated with bacterial lipopolysaccharide and interferon gamma. alpha-MSH inhibited production of NO, as estimated from nitrite production and nitration of endogenous macrophage proteins. This occurred through inhibition of production of NO synthase II protein; steady-state NO synthase II mRNA abundance was also reduced. alpha-MSH increased cAMP accumulation in RAW cells, characteristic of alpha-MSH receptors in other cell types. RAW cells also expressed mRNA for the primary alpha-MSH receptor (melanocortin 1). mRNA for proopiomelanocortin, the precursor molecular of alpha-MSH, was expressed in RAW cells, and tumor necrosis factor alpha increased production and release of alpha-MSH. These results suggest that the proinflammatory cytokine tumor necrosis factor alpha can induce macrophages to increase production of alpha-MSH, which then becomes available to act upon melanocortin receptors on the same cells. Such stimulation of melanocortin receptors could modulate inflammation by inhibiting the production of NO. The results suggest that alpha-MSH is an autocrine factor in macrophages which modulates inflammation by counteracting the effects of proinflammatory cytokines.Proceedings of the National Academy of Sciences 09/1995; 92(17):8016-20. · 9.74 Impact Factor
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ABSTRACT: The effect of α-melanocyte stimulating hormone (α-MSH) on colonic inflammation in the rat. In this study, we investigated the effects of α-MSH administration on trinitrobenzene sulfonic acid-induced colitis and the role of nitric oxide and prostaglandins in this response. α-MSH treatment (25 μg/rat, intraperitoneally; twice daily for 3 days) reduced the colonic macroscopic lesions compared to untreated ones in both acute and chronic colitis groups. This effect was reversed by pretreatment with the nitric oxide donor, sodium NP (4 mg/kg, intravenously) or cyclooxygenase-1 selective antagonist indomethacin (5 mg/kg, subcutaneously) in the acute group and with the cyclooxygenase-2 selective antagonist nimesulide (3 mg/kg, subcutaneously) in the chronic group. α-MSH had no effect on colonic wet weight and myeloperoxidase acitivity compared to the untreated colitis group. However, protein oxidation was markedly elevated in the α-MSH-treated group compared to untreated ones. Nitroprusside and indomethacin reversed the effect of α-MSH on macroscopic lesions in the acute groups, whereas nimesulide showed a similar effect in the chronic group. In conclusion, the results of our study show a protective role of α-MSH on colonic lesions which partially involves nitric oxide and prostaglandins.Peptides. 01/2000;
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ABSTRACT: In this study the role of free radicals and lipid peroxidation as mediators of chemically induced mucosal damage was investigated. Two enzymatic antioxidants, superoxide dismutase or catalase injected intravenously, reduced mucosal damage either by ethanol or aspirin. Of six nonenzymatic antioxidants, given in a wide dose range subcutaneously 30 min before intragastric administration of absolute ethanol, only propyl gallate decreased mucosal damage, while four of the antioxidants tested against aspirin were protective. These nonenzymatic antioxidants were antisecretory in the pylorus-ligated rat. The concentration of conjugated dienes and malondialdehyde measured in the gastric mucosa shortly after ethanol or aspirin administration remained unchanged or slightly decreased. These results indicate that free radicals may be involved in the pathogenesis of acute gastric mucosal injury caused by chemicals, but their mechanisms of action probably does not involve lipid peroxidation.Digestive Diseases and Sciences 01/1988; 32(12):1395-401. · 2.26 Impact Factor