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

Helicobacter pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) are major pathogenic factors in peptic ulcer disease but whether these two factors exert synergistic or antagonistic effects on ulcer healing has been a subject of controversy. We compared the effect of aspirin alone with that of aspirin combined with H. pylori on gastric acid secretion and healing of acetic acid gastric ulcers in rats. The H. pylori colonization of gastric mucosa was determined by viable H. pylori culture, histology and assessment of bacterial DNA using polymerase chain reaction (PCR). The area of ulcers, gastric blood flow, mucosal generation of prostaglandin E(2) and plasma gastrin levels and expression of cyclooxygenase-1, cyclooxygenase-2 and growth factors was determined. Aspirin delayed significantly the healing of chronic gastric ulcers, decreased the gastric blood flow at the ulcer margin and gastric mucosal prostaglandin E(2) generation being without significant influence on gastric acid output. H. pylori acquisition that produced moderate gastric inflammation at the ulcer margin delayed significantly the healing of gastric ulcers, decreased significantly both the gastric blood flow at the ulcer margin and the gastric secretion while raising significantly the gastric mucosal prostaglandin E(2) generation and plasma gastrin levels. H. pylori infection attenuated the aspirin-induced inhibition of ulcer healing and accompanying fall in the gastric blood flow. Both aspirin and H. pylori up-regulated significantly cyclooxygenase-2 messenger RNA (mRNA) and protein but not that of cyclooxygenase-1 at the ulcer margin. Aspirin reduced significantly the transforming growth factor alpha- and vascular endothelial growth factor mRNAs, but these effects were significantly attenuated by H. pylori. We conclude that H. pylori antagonizes, in part, aspirin-induced delay of ulcer healing due to suppression of acid secretion, the enhancement in prostaglandin E(2) possibly derived from cyclooxygenase-2 and the overexpression of transforming growth factor alpha and vascular endothelial growth factor in the ulcer area.
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PMID:Effect of Helicobacter pylori on delay in ulcer healing induced by aspirin in rats. 1223 91

The influence of central and peripheral stimuli on gastric acid secretion is mediated via activation of histaminergic, gastrinergic, and cholinergic pathways coupled to intracellular second-messenger systems that determine the trafficking and activity of H+ K+-ATPase, the proton pump of the parietal cell. Histamine, released from enterochromaffin-like cells stimulates the parietal cell directly via H-2 receptors coupled to generation of cAMP. Gastrin, acting via cholecystokinin-2 receptors on enterochromaffin-like cells coupled to an increase in intracellular calcium, stimulates the parietal cell indirectly by activating histidine decarboxylase, releasing histamine, and inducing enterochromaffin-like cell hypertrophy and hyperplasia. Acetylcholine, released from gastric postganglionic intramural neurons, stimulates the parietal cell directly via M-3 receptors coupled to intracellular calcium release and calcium entry. The second-messenger systems activated in the parietal cell converge on H+ K+-ATPase that catalyzes the exchange of luminal K+ for cytoplasmic H+ and is responsible for gastric luminal acidification. The main inhibitor of acid secretion is somatostatin which, acting via sst2 receptors, exerts a tonic inhibitory influence on parietal, enterochromaffin-like, and gastrin cells. Acute infection with Helicobacter pylori results in hypochlorhydria, whereas chronic infection may be associated with either hypo- or hyperchlorhydria. Although prostaglandins are thought to play a physiologic role in the regulation of acid secretion and maintenance of gastric mucosal integrity, the precise roles of cyclooxygenase-1 and cyclooxygenase-2 in these processes still eludes us.
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PMID:Gastric secretion. 1703 Dec 7