Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038358 (gastric ulcer)
 5,179 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

New developments in the study of the pathogenesis of experimental gastric and duodenal ulcers indicate a complex multifactorial process leading to ulceration. The concept of gastric cytoprotection with prevention of hemorrhagic mucosal lesions by PG, SH, or other compounds without inhibiting acid secretion was discovered while investigating animal models of gastric erosions and ulcers. Subsequent research into the pathophysiology of gastric ulcer has been revitalized. New studies have demonstrated that the development or prevention of vascular injury in the gastric mucosa plays a crucial role in gastric mucosal injury and protection. The pathophysiology of experimental duodenal ulcer disease has shown that controlling gastric acid secretion is not the only approach to the prevention or treatment of this disorder. Data from human and animal experiments suggest that duodenal dysmotility contributes to the decreased neutralization of acid whether secreted at a normal or subnormal rate, in the duodenal bulb. Dopamine infusion corrected experimentally induced duodenal hypermotility, but other neurotransmitters may also be involved. Multidisciplinary investigations using experimental models of gastric and duodenal ulcers lead not only to the discovery of new concepts and pathogenetic mechanisms but also to the recognition of new chemicals that may exert gastroprotective and antiulcerogenic effects.
 ...
PMID:Experimental gastric and duodenal ulcers. Advances in pathogenesis. 218 31

The physiological roles of sympathetic nerve system in the stomach has been thought to be very important in the pathogenesis of peptic ulceration. The aim of this study was to examine the effects of dopamine receptor agonists and antagonists on gastric acid secretion and gastroduodenal ulcer formation induced by cysteamine injection in rats. Cysteamine was given by subcutaneous injection as 400mg/kg in doses. Dopamine was given by continuous iv infusion as 2, 4 and 8 micrograms/kg/min in doses. Domperidone regarded as antagonists of D2 receptor was given by continuous iv infusion as 2 micrograms/kg/min in doses. As a result of acid output measured during infusion of dopamine alone or dopamine with domperidone in non-vagotomized or vagotomized rats, increasing effects of dopamine on acid output were depended on dopaminergic mechanism, and decreasing effects of dopamine on acid output were depended on dopaminergic mechanism in rami vagus. As a result of duodenal and gastric ulcer index, ulcerogenicity of cysteamine in the stomach was concerned with dopaminergic mechanism more than that of in the duodenum. These results suggested that the pathogenesis of experimental ulcer induced by cysteamine injection was depended on dopamine receptor in the stomach.
 ...
PMID:[Effects of dopamine receptor agonists and antagonists on an experimental ulcer system induced by cysteamine in rats--dopaminergic mechanism vs pathogenesis of peptic ulceration]. 318 69

The lifetime prevalence of duodenal ulcer in the United States is 8 to 10%, whereas another 1% of the population is affected by gastric ulcer. Both central and peripheral dopamine pathways may influence ulcer pathogenesis. Dopamine agonists prevent whereas antagonists augment stress- and chemically induced gastrointestinal ulcers in preclinical models. The dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,36-tetrahydropyridine (MPTP) depletes central dopamine and induces lesions in the substantia nigra, and, if given in high doses, MPTP induces a Parkinson disease-like syndrome and gastric ulcers. Because schizophrenia is attributed, in part, to an overactive dopaminergic system, persons with schizophrenia may display a reduced susceptibility toward gastrointestinal ulcers. A case-control study was conducted in patients represented in the 2002 National Inpatient Sample, the largest all-payer inpatient care database in the United States, consisting of 5 to 8 million inpatient hospital stays per year, which approximates a 20% sample of community hospitals. A significant association was observed between schizophrenia and diminished risk for duodenal (odds ratio [OR] 0.55; 95% confidence interval [CI] 0.45-0.67) and gastric (OR 0.54; 95% CI 0.46-0.63) (p < .01) ulcers but not for gastrojejunal ulcers (OR 0.44; 95% CI 0.16-1.20) (p = .11). Potential confounders such as age, gender, race, tobacco or alcohol dependence, and Helicobacter pylori infection were controlled in multivariate analyses. This observational study in a large sample of patients in community hospitals suggests that schizophrenia and attendant neurobiologic mechanisms (eg, variability in dopamine pathways) may act in concert to modify the composite risk for gastrointestinal ulcers. Dopamine pathways warrant further prospective research as new potential drug targets in ulcer disease.
 ...
PMID:Cosegregation of gastrointestinal ulcers and schizophrenia in a large national inpatient discharge database: revisiting the "brain-gut axis" hypothesis in ulcer pathogenesis. 1796 81

Dopamine is linked to gastrointestinal functions. However, its exact nature in stress-induced gastric pathology is still not clear. In the present study, an attempt has been made to identify the effects of dopamine in stress-induced gastric ulcers, and concurrent alterations in various ulcer-influencing factors such as plasma corticosterone levels, gastric mucosal PGE(2) content and proton pump activity. The dopamine D(1) receptor agonist (A 68930) and antagonist (SCH 23390), and D(2) receptor agonist (quinpirole) and antagonist (sulpiride) were used to evaluate their effects on acute stress (single immobilization for 150 min) and chronic unpredictable stress (two different types of stressors for 7 days) induced gastric ulcers in rats. Acute and chronic unpredictable stress significantly increased the gastric ulcer severity, adrenal hypertrophy and corticosterone levels, while gastric mucosal dopamine levels were decreased. Pretreatment of sulpiride (60 mg/kg) significantly reverted the acute stress-induced alterations, while A 68930 (0.25mg/kg) significantly restored the acute and chronic unpredictable stress-induced alterations. In contrast, administration of SCH 23390 (0.1-0.5mg/kg) and quinpirole (0.1-0.5mg/kg) failed to alter acute stress-induced alterations. Further, A 68930 and sulpiride showed different response on proton pump inhibition under in-vitro condition. A 68930 (10-50 microg/ml) inhibited the gastric H(+) K(+)-ATPase activity comparable to positive control omeprazole, while sulpiride (10-50 microg/ml) had no effect. A 68930 also normalized the decreased gastric PGE2 content observed during chronic unpredictable stress. The histopathological evaluation of gastric mucosal tissue supported the observations regarding the gastroprotective effect of sulpiride during acute stress and of A 68930 during both acute and chronic unpredictable stress conditions. Our results provide important insights into the mechanism of dopamine-regulated pathways, which cause an overall pathophysiology of gastric stress ulcers and implicating the importance of D(1) agonist in ulcer protection. Thus, current study highlights the need to evaluate anti-stress and anti-ulcer agents in terms of their ability to modulate dopaminergic transmissions.
 ...
PMID:Differential response of A 68930 and sulpiride in stress-induced gastric ulcers in rats. 2059 13