gastrin-releasing-peptide and Peptic-Ulcer

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

Topics: Animals; Gastric Acid; Gastrin-Releasing Peptide; Gastrins; Histamine Antagonists; Humans; Ligands; Peptic Ulcer; Receptor, Cholecystokinin B; Receptors, Bombesin; Receptors, Histamine H3

The authors present a review of the role of psychological factors in peptic ulcer disease (PU). Three lines of research have been identified: personality, psychological factors and PU; stressful life events and their relationship to PU; possible interactions between biological parameters, the CNS and psychosocial aspects. The analysis of the studies presented shows that there is a certain level of agreement with regard to personality and psychological aspects; PU patients present a personality with dependence/independence problems and high level of anxiety. Data concerning the role of stress appear to be far from uniform and often even contradictory. Much remains to be done with respect to the possible links between psychological and biological parameters; there have been only few studies in man--which have not been duplicated and were performed on a limited number of patients--but a fair number in animals. However, the results concerning the relationship between psyche and secretory patterns are very interesting, and represent one of the most important lines of future research.

Topics: Animals; Bombesin; Gastric Acid; Gastrin-Releasing Peptide; Humans; Hypothalamus; Life Change Events; Neurotic Disorders; Peptic Ulcer; Peptides; Personality; Psychophysiologic Disorders; Stress, Psychological; Suicide; Thyrotropin-Releasing Hormone; Trimipramine

We have studied the basal release of cholecystokinin (CCK) and the CCK response to gastrin-releasing peptide (GRP) in man. GRP infusion was followed by a substantial and immediate release of CCK. Pancreatico-duodenectomy or antrectomy with or without duodenal exclusion or antrectomy with truncal vagotomy did not significantly change the basal release of CCK or the GRP-induced CCK release. These results indicate that both basal and GRP-induced release of CCK predominantly originate from the small intestine below the duodenum and the upper part of the jejunum and is unchanged by duodenal exclusion and vagal denervation of the small intestine.

Topics: Cholecystokinin; Duodenum; Female; Gastrin-Releasing Peptide; Gastrointestinal Hormones; Humans; Infusions, Parenteral; Male; Middle Aged; Pancreas; Peptic Ulcer; Peptides; Pyloric Antrum; Vagotomy, Truncal

Topics: Autonomic Nervous System; Campylobacter; Cell Cycle; Gastric Acid; Gastric Mucosa; Gastrin-Releasing Peptide; Gastrins; Humans; Microcirculation; Pepsin A; Peptic Ulcer; Peptides; Prostaglandins; Secretin

Topics: Gastric Acid; Gastrin-Releasing Peptide; Gastrins; Gastrointestinal Hormones; Humans; Peptic Ulcer; Peptides; Somatostatin

Topics: Animals; Gastrin-Releasing Peptide; Immersion; Male; Peptic Ulcer; Peptides; Rats; Rats, Inbred Strains; Regional Blood Flow; Stomach; Stress, Physiological

Gastrin releasing peptide(GRP)-like immunoreactivity in human plasma was measured using radioimmunoassay of neuromedin C (NMC) in 83 healthy and 58 diseased subjects. In the healthy group, the mean value of fasting GRP-like immunoreactivity was 2.1 +/- 1.4 (mean +/- SD) pmol/L. There was a slight positive correlation between the GRP-like immunoreactivity values and aging. Postprandial serial measurements demonstrated that GRP-like immunoreactivity showed no response to a significant elevation of serum gastrin concentration. The group with chronic renal failure on hemodialysis gave the highest value, 7.1 +/- 2.1 pmol/L (p less than 0.01). There were no statistical differences between the healthy controls and groups with peptic ulcer, liver cirrhosis, diabetes mellitus or carcinomas, although some cancer patients had a marked increase in GRP-like immunoreactivity value.

Topics: Adult; Aged; Bombesin; Diabetes Mellitus; Female; Gastrin-Releasing Peptide; Gastrins; Humans; Kidney Failure, Chronic; Liver Cirrhosis; Male; Middle Aged; Neoplasms; Peptic Ulcer; Peptide Fragments; Peptides; Radioimmunoassay