Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ghrelin, identified in the gastric mucosa has been involved in control of food intake and growth hormone (GH) release but little is known about its influence on gastric secretion and mucosal integrity. The effects of ghrelin on gastric secretion, plasma gastrin and gastric lesions induced in rats by 75% ethanol or 3.5 h of water immersion and restraint stress (WRS) were determined. Exogenous ghrelin (5, 10, 20, 40 and 80 microg/kg i.p.) increased gastric acid secretion and attenuated gastric lesions induced by ethanol and WRS and this was accompanied by the significant rise in plasma ghrelin level, gastric mucosal blood flow (GBF) and luminal NO concentrations. Ghrelin-induced protection was abolished by vagotomy and attenuated by suppression of COX, deactivation of afferent nerves with neurotoxic dose of capsaicin or CGRP(8-37) and by inhibition of NOS with L-NNA but not influenced by medullectomy and administration of 6-hydroxydopamine. We conclude that ghrelin exerts a potent protective action on the stomach of rats exposed to ethanol and WRS, and these effects depend upon vagal activity, sensory nerves and hyperemia mediated by NOS-NO and COX-PG systems.
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PMID:Exogenous and endogenous ghrelin in gastroprotection against stress-induced gastric damage. 1517 19

Exogenous prostaglandins (PG) applied in small gastroprotective doses fail to affect healing of gastro-duodenal ulcers but accelerate the healing when used in larger gastric inhibitory doses that appear to enhance COX-2 expression and PGE(2) generation in the ulcer area. COX-1 and COX-inhibitors delay ulcer healing, particularly when both COX isoforms are suppressed such e.g. by indomethacin. Dexamethasone, that decreases the expression of COX-2 and mucosal generation of PGE(2), delays ulcer healing that can be reversed by the addition of small dose of exogenous PGE(2). Proton pump inhibitors (PPI) such as omeprazole and PGE analogs, accelerate ulcer healing mainly due to potent inhibition of gastric acid secretion, but they also augment the COX-2 expression and enzyme activity in the ulcerated mucosa. Endogenous PG generated at ulcer margin appear to be involved in ulcer healing promoted by growth factors and gut hormones such as gastrin or CCK and melatonin acting, at least in part, through increase of induction of COX-2 and local release of PGE(2) in the ulcer area. The ulcer healing activity of growth factors (e.g. EGF, TGF alpha, HGF) and certain gut hormones (gastrin, CCK) as well as melatonin, can be attenuated by treatment with COX-1 or COX-2 inhibitors which suppress the release of PGE(2) but enhance the expression of COX-2. It is concluded that endogenous PG originating mainly from upregulated COX-2 at the ulcer margin play crucial role in ulcer healing by exogenous PG, PPI, growth factors, gut hormones and melatonin, while COX-1 and COX-2 inhibitors delay ulcer healing by suppressing PG generation, and increasing COX-2 expression in the ulcer area.
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PMID:Prostaglandins and ulcer healing. 1624 87

The formation of acute gastric lesions depends upon the balance between the aggressive factors promoting mucosal damage and the natural defense mechanisms. Previous studies have shown that melatonin inhibits gastric acid secretion, enhances the release of gastrin, augments gastric blood flow (GBF), increases the cyclooxygenase-2 (COX-2)-prostaglandin (PG) system and scavenges free radicals, resulting in the prevention of stress-induced gastric lesions. Besides the pineal gland, melatonin is also generated in large amounts in the gastrointestinal tract and due to its antioxidant and anti-inflammatory properties; this indole might serve as local protective endogen preventing the development of acute gastric damage. The results of the present study indicate that stress-induced gastric lesions show circadian variations with an increase in the day time and a decline at night. These changes are inversely related to plasma melatonin levels. Following pinealectomy, stress-induced gastric mucosal lesions were more pronounced both during the day and at night, and were accompanied by markedly reduced plasma melatonin levels with a pronounced reduction in mucosal generation of prostaglandin E(2) (PGE(2)), GBF and increased free radical formation and by small rise in plasma melatonin during the dark phase. We conclude that stress-induced gastric ulcerations exhibit a circadian variation with an increase in the day and attenuation at night and that these fluctuations of gastric stress ulcerogenesis occur also after pinealectomy, depending upon the interaction of COX-PG and free radicals, probably mediated by the changes in local gastric melatonin.
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PMID:Day/night differences in stress-induced gastric lesions in rats with an intact pineal gland or after pinealectomy. 1808 46

Orexin-A, identified in the neurons and endocrine cells in the gut, has been implicated in control of food intake and sleep behavior but little is known about its influence on gastric secretion and mucosal integrity. The effects of orexin-A on gastric secretion and gastric lesions induced in rats by 3.5 h of water immersion and restraint stress (WRS) or 75% ethanol were determined. Orexin-A (5-80 microg/kg i.p.) increased gastric acid secretion and attenuated gastric lesions induced by WRS and this was accompanied by the significant rise in plasma orexin-A, CGRP and gastrin levels, the gastric mucosal blood flow (GBF), luminal NO concentration and an increase in mRNA for CGRP and overexpression of COX-2 protein and the generation of PGE(2) in the gastric mucosa. Orexin-A-induced protection was abolished by selective OX-1 receptor antagonist, vagotomy and attenuated by suppression of COX-1 and COX-2, deactivation of afferent nerves with neurotoxic dose of capsaicin, pretreatment with CCK(2)/gastrin antagonist, CGRP(8-37) or capsazepine and by inhibition of NOS with L-NNA. This study shows for the first time that orexin-A exerts a potent protective action on the stomach of rats exposed to non-topical ulcerogens such as WRS or topical noxious agents such as ethanol and these effects depend upon hyperemia mediated by COX-PG and NOS-NO systems, activation of vagal nerves and sensory neuropeptides such as CGRP released from sensory nerves probably triggered by an increase in gastric acid secretion induced by this peptide.
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PMID:Gastroprotective action of orexin-A against stress-induced gastric damage is mediated by endogenous prostaglandins, sensory afferent neuropeptides and nitric oxide. 1837 17

Melatonin is a potent reactive oxygen metabolite scavenger and antioxidant that has been shown to influence many physiological functions of the gastrointestinal (GI) tract including secretion, motility, digestion and absorption of nutrients. The role of melatonin in gastroduodenal defense and ulcer healing has been the subject of recent investigations. Melatonin produced in the GI mucosa plays an important role in protection against noxious agents thus contributing to the maintenance of GI integrity and to esophageal protection, gastroprotection and ulcer healing. This review was designed to summarize the involvement of melatonin, conventionally considered as a major hormone of the pineal gland, in the maintenance of gastric mucosal integrity, gastroprotection, ulcer healing and intestinal disorders. Melatonin was originally shown to attenuate gastric mucosal lesions but controversy exists in the literature as to whether melatonin derived from the pineal gland, considered as the major source of this indole, or rather gastrointestinal melatonin plays predominant role in gastroprotection. Intragastric and central administration of exogenous melatonin and L-tryptophan, this indoleamine precursor, affords protection against gastric hemorrhagic damage caused by the exposure of gastric mucosa to variety of non-topical and topical ulcerogens such as stress, ethanol and ischemia-reperfusion. The speed of ulcer healing in experimental animals and humans is accelerated by melatonin. This indoleamine could be also effective against the esophageal lesions provoked by reflux esophagitis in animal models and prevents the incidence of GERD in humans. The melatonin-induced gastroprotection is accompanied by an increase in gastric blood flow, plasma melatonin concentration, enhancement in mucosal generation of PGE2, luminal NO content and plasma gastrin levels. Melatonin scavenges reactive oxygen metabolites, exerts anti-oxidizing and anti-inflammatory actions and inhibits the formation of metalloproteinases- 3 and -9; both implicated in the pathogenesis of gastrointestinal injury and formation of gastric ulcers. Blockade of MT2 receptors by luzindole, significantly attenuated melatonin- and L-tryptophan-induced protection and increased the speed of ulcer healing and these effects were accompanied by an increase in the GBF and luminal content of NO suggesting that melatonin exhibits gastroprotection and hyperemia via activation of MT2 receptors and release of NO. The accumulated evidence indicates that the melatonin-induced gastroprotection and the enhancement in healing rate of gastric ulcers may involve the gastroprotective factors derived from the activation of PG/COX and NO/NOS systems as well as gastrin which also was shown to exhibit protective and trophic effects in the upper GItract. Interestingly, pinealectomy, which suppressed plasma melatonin levels, markedly exacerbated gastric lesions induced by topical and non-topical ulcerogens and these effects are counteracted by a concurrent supplementation with melatonin. Evidence is provided that exogenous melatonin and that converted from its precursor, L-tryptophan, attenuates acute gastric lesions and accelerates ulcer healing via interaction with MT2 receptors due to an enhancement of gastric microcirculation, probably mediated by NO and PG derived from NOS and COX-1 and COX-2 overexpression and activity. The pineal gland plays an important role in the limitation of gastric mucosal injury and the acceleration of ulcer healing via releasing endogenous melatonin, which attenuates oxidative stress and exerts anti-inflammatory action.
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PMID:Mechanisms of esophageal protection, gastroprotection and ulcer healing by melatonin. implications for the therapeutic use of melatonin in gastroesophageal reflux disease (GERD) and peptic ulcer disease. 2425 71