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)

The gastrointestinal tract is the largest endocrine organ in the body. However, gastrointestinal hormones are not confined to the gut and many of them are delivered to their target tissue by neural and paracrine routes as well as the circulation. Regulatory peptide is therefore a more appropriate term than gastrointestinal hormone. The functions of these regulatory peptides include effects on intake, digestion and absorption of food, and changes in gut secretions, motility and growth. Since these peptides do not act alone but in concert it has been difficult to ascribe particular functions to individual peptides. However, the recent and on-going development of specific regulatory peptide agonists and antagonists has resulted in major advances in our understanding of the physiology of these peptides. In turn these findings are creating new therapeutic avenues providing some return from all the research on these gastrointestinal regulatory peptides. The somatostatin derivative (octreotide or sandostatin) is the most obvious example. Although only approved in Australia for treatment of carcinoids and VIPomas, the prospects include treatment of other gastroenteropancreatic tumours, acromegaly, idiopathic diarrhoea, fistula closure, dumping, and ERCP or post-operative pancreatitis. A new gastrokinetic agent, that acts via the motilin receptor, is undergoing trials for the treatment of impaired gastric emptying. The trophic effect of gastrointestinal peptides has clinical significance. For instance, gastrin antagonists inhibit cell proliferation of colon carcinoma cell lines. Furthermore the trophic effect of gastrin must be considered when potent gastric acid inhibitors, which cause a reflex increase in gastrin, are used. The outlook is for more mammalian regulatory peptides to be discovered adding further to the complexity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gastrointestinal hormones: from basic science to a clinical perspective. 220 81

The primary factors in feeding premature infants are dependent on the development and maturation of digestion and absorption. The maturation of digestive and absorptive functions of carbohydrates, proteins, fats, minerals, and vitamins in the young premature infant were determined in relation to availability of hydrolytic enzymes, such as lipases, proteases, amylases, glucosidases, and lactase. The feeding is dependent on the ability of the premature infant to secrete salivary enzymes, gastric acid, pepsin, pancreatic exocrine enzymes, the presence of enterohepatic circulation, and the hydrolytic and absorptive capacity of the entercocyte. To evaluate the complexity of the gut maturation process, we proposed a unified concept where the ontogeny of the gastrointestinal system is the result of the following four major determinants: genetic endowment, intrinsic developmental and biological clock, endogenous regulatory mechanisms, and environmental influences. The developmental clock represents a predetermined temporal sequence of happenings in ontogeny that is inherently controlled. By 20 weeks of gestation, the anatomic differentiation of the fetal gut has progressed to the extent that it resembles that of a newborn. Secretory and absorptive functions, however, develop at different rates; the intestinal absorptive process is only partially available before 26 weeks of gestation, whereas gastric and pancreatic secretion is only basal and can be stimulated only partially even in the full-term newborn period. Regulatory mechanisms control the expression of the genetic endowment at various stages in gastrointestinal development. Neural-hormonal factors play major roles in the ontogeny of the gut. Adrenalectomy, hypophysectomy, and thyroidectomy delay the development of the gut. Administration of glucocorticoids or thyroxine at the critical stage in maturation causes early appearance of enzymes within the intestine. Other hormones that are potentially important in regulating gastrointestinal development include cholecystokinin, gastrin, secretin, which have trophic effects on the gastrointestinal tract, and insulin, insulin-like growth factors, and epidermial growth factor. The development of gastrointestinal secretory function, particularly in response to hormonal stimulation, has received considerable attention. The degree of response of the target cell is determined not only by the amount of effective hormone reaching it but also by the number and affinity of receptors on its surface. Human newborns have high levels of gastrin in their sera, yet have low acid output. Exogenous gastrin is an ineffective stimulant despite the presence of seemingly "anatomically developed" parietal cells. It seems that neither endogenous nor exogenous gastrin has an effect on the target cell. If one accepts the role of circulating gastrin levels in the regulation of its own receptor, one can hypothesize the absence of a regulatory effect of gastrin in the newborn period. It was shown that hormonal regulation of migrating activity by motilin is also absent in the preterm and term infant. Plasma levels of motilin in neonates are comparable to those found in adults, but migrating motor complexes occur in the absence of cycling of plasma concentrations. Interestingly, however, the motilin receptor appears to be present. In conclusion, the feeding mode content, concentration, and volume of the very young premature infant can be assessed by the development of digestive and absorptive capacity and gut motility. The concomitant changes in gut hormones and regulatory peptides during ontogeny and feeding will add a new dimension in the understanding of when, what, and how to feed the very young premature infant.
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PMID:The ontogeny of the small intestinal epithelium. 1048 84

Erythromycin, an antibiotic agent, is known to be a motilin receptor agonist. Motilin is a peptide hormone that regulates gastric motility. One of the gastrointestinal motility regulatory factors has been assumed to be the induction of changes in the levels of peptides (gastrin, somatostatin and motilin) in plasma. We have elucidated the effects of erythromycin by examining changes in the plasma levels of gastroinitestinal peptides. In this study, we investigated the effects of erythromycin on the plasma levels of gastrointestinal peptides (somatostatin, motilin, and gastrin) in healthy volunteers and patients with delayed gastric emptying (DGE). After a single oral administration, erythromycin caused a significant increase in plasma gastrin-like immunoreactive substance (IS) levels at 60 min. But the agent did not alter the levels of somatostatin- and motilin-IS. DGE is the most frequent postoperative complication after pylorus-preserving pancreatoduodenectomy. Molitin is assumed to be one important factor that influences DGE. We also examined the effects of erythromycin on the plasma motilin-IS levels of postoperative patients. The plasma motilin-IS levels were increased after 1 week of oral administration of erythromycin compared with preadministration. These results suggest that the pharmacologic effects of erythromycin in promoting gastric emptying are closely related to changes in plasma motilin-IS levels.
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PMID:Effects of erythromycin on plasma gastrin, somatostatin, and motilin levels in healthy volunteers and postoperative cancer patients. 1599 21

Although proton pump inhibitors have become the mainstay of treatment in gastro-oesophageal reflux disease (GORD), there are still unmet needs in the management of this very common disorder. For example, all current proton pump inhibitors have a relatively slow onset of action and their activity is limited mainly to the post-prandial period with far less effective inhibition of nocturnal acid secretion. In order to achieve more potent, rapid and sustained acid inhibition several compounds are currently under development, such as new proton pump inhibitors with a prolonged plasma half-life, potassium competitive ATPase blockers (PCABs), histamine H3 agonists, and gastrin antagonists. Acid suppression does not, however, cure the disease and relapses are frequently observed after discontinuation of proton pump inhibitor therapy. Among the different abnormalities involved in the pathophysiology of this multifactorial disease, transient lower oesophageal sphincter relaxations represent the major mechanism responsible for episodes of reflux. Baclofen, the prototype GABA(B) receptor agonist, is one of the most potent inhibitors of transient lower oesophageal sphincter relaxations identified. To date the transfer of these relaxation-controlling pharmacological agents into clinical practice has however been hampered by the occurrence of unacceptable side effects. Beside "anti-relaxation therapy", the potential of novel prokinetics such as motilin agonists has been explored, especially since the motilin receptor has been cloned. Thus far the broad therapeutic value of prokinetics in GORD does, however, seem very limited in terms of efficacy with respect to oesophageal motility and acid exposure. Lastly, further research is necessary to better understand the complex mechanisms involved in oesophageal sensitivity and mucosal defence.
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PMID:Pharmacological targets in gastro-oesophageal reflux disease. 1636 47