Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0013395 (dyspepsia)
 4,879 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Liver affects the release and clearance of many hormones, but the interactions between gastrointestinal peptides and liver function are obscure. Aim of this study was to evaluate plasma concentrations of gastrointestinal peptides during acute hepatic cytonecrosis and during liver regeneration in man. The study was performed in ten patients with viral hepatitis (8 virus A, 2 virus B) in the acute phase (alanine transaminase = 3073 +/- 739 U/L; mean +/- SEM), and at days 7, 45 and 52 after the initial evaluation, during clinical and biochemical recovery (52nd day, alanine transaminase = 77 +/- 26). Plasma concentrations of the following hormones were evaluated by radioimmunoassay: glucagon, insulin, gastrin, vasoactive intestinal peptide, bombesin, neurotensin, cholecystokinin, secretin and motilin. Only serum bombesin and cholecystokinin were significantly (p < 0.01) increased in the acute phase of hepatitis (bombesin: 138 +/- 21 pg/ml; cholecystokinin: 57 +/- 7 pg/ml); they returned to normal values during convalescence (bombesin: 60 +/- 8; cholecystokinin: 31 +/- 4). During hepatocellular necrosis, plasma concentrations of cholecystokinin and bombesin, which are both cellular growth factors and regulatory signals of food introduction and satiety state, were increased by 83% and 130%, respectively. Increase of these hormones may cause the dyspepsia and lack of appetite that characterizes the initial phase of acute viral hepatitis.
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PMID:Gastrointestinal peptide hormones in acute viral hepatitis. 878

Most patients with peptic ulcer disease are currently treated with proton pump inhibitors or histamine H(2) receptor antagonists. The long-term use of these compounds has been associated with two potential problems. Firstly, proton pump inhibitors may induce enterochromaffin-like (ECL) cell hyperplasia. Secondly, ulcers may relapse despite maintenance therapy with histamine H(2) antagonists. This has been the rationale for the development of new antisecretory agents, including antagonists against gastrin and gastrin releasing peptide (GRP), as well as ligands to histamine H(3) receptors. Several potent, high affinity cholecystokinin (CCK)-2 receptor antagonists have recently been identified such as L-365260, YM-022, RP-73870, S-0509, spiroglumide and itriglumide (CR-2945). Current data suggest that they all have antisecretory and anti-ulcer effects. In addition to reducing acid production, CCK-2 receptor antagonists may possibly also accelerate gastric emptying, a combination of functions which could potentially be beneficial in patients with functional dyspepsia. Receptors for bombesin and its mammalian counterpart GRP have been localised in the brain, spinal cord and enteric nerve fibres of the gut as well as on secretory cells and smooth muscle cells of the intestinal tract. Current data clearly indicate that endogenous GRP is involved in the regulation of basal and postprandial acid secretion. However, at this stage it is not clear whether GRP agonists or GRP antagonists can be developed into useful drugs. The peptide has a wide range of biological effects and it is likely that analogues of GRP or antagonists of the peptide affect not only gastric acid secretion but also induce considerable side effects. Histamine plays a central role in the stimulation of acid secretion. After their detection in the brain, H(3) receptors have been identified in a variety of tissues including perivascular nerve terminals, enteric ganglia of the ileum and lung, and ECL cells. Despite many studies, the role of H(3) receptors in the regulation of gastric acid secretion is still unclear. Controversial data have been presented, and study results largely depend on the species and experimental models. It seems unlikely that proton pump inhibitors or H(2) receptor antagonists will be replaced in the near future by new antisecretory agents. The current shortcomings of the new compounds include mainly their reduced clinical effectiveness and pharmacological limitations. However, the development of these new antisecretory compounds provides interesting tools to assess the physiological and pharmacological role of different receptors within the gastrointestinal tract. The use of CCK-2 receptor antagonists in patients with functional dyspepsia and Zollinger-Ellison syndrome should be examined in randomised, controlled trials.
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PMID:New molecular targets for treatment of peptic ulcer disease. 1292 85