[Polypeptide hormones in gastrointestinal tract].
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Numerous GI hormones and peptides, such as gastrin, CCK, secretin, glucagon, somatostatin and EGF, have been shown to stimulate at least part of the trophic response in GI tissues. Whether any of these (or a different one) accounts for gastrointestinal adaptation is unknown. Final proof will entail the demonstration that the endogenous serum levels of one of these increases during the adaptation period to amounts significant to cause the response.
This is a critical survey of the results of recent investigations on gastrointestinal peptide hormones. The following subjects are dealt with: molecular homology and heterogeneity; mechanism of action of gastrointestinal peptide hormones; hormone-receptor binding; trophic effect; metabolism of gastrointestinal peptide hormones; relationship between humoral and neural regulation in the nervous system.
UNLABELLED: Aim of this study was to investigate how gastrointestinal hormones such as exogenous s.c. caerulein (6 micrograms/kg body weight), secretin (100 U/kg body weight), bombesin (20 micrograms/kg body weight, s.c.), CCK-8 (10 micrograms/kg body weight, i.p.), the CCK-A receptor antagonist L 364,718 (100 micrograms/kg body weight, i.p.), camostate (400 mg/kg body weight per os) which releases endogenous CCK and the coadministration of camostate with atropin (250 micrograms/kg body weight, s.c) or L 364,718 (1 mg/kg) influence milk intake from nipples, gastric emptying, and discharge of pancreatic trypsin content in 10-day-old rat pups. Saline-treated pups served as controls. The non-fasting Wistar rat pups of both sexes were used in littermate order. The suckling lasted for 30 and 45 min, respectively. One pup was used only once. After suckling the pups were decapitated, their stomach and pancreas were removed and weighed. The gastric food content was regarded as intake of milk and expressed as difference between the filled minus empty stomach. Pancreatic trypsin and protein content, plasma CCK level were measured. The exogenous agents did not influence gastric content. The investigated peptides decreased, L 364,718, however, increased the pancreatic trypsin/protein ratio. Camostate increased gastric content by 60% and decreased pancreatic trypsin/protein ratio vs saline by 90%. The gastric and pancreatic effects of camostate were not reversed by atropine or L 364,718. CONCLUSION: Exogenous and endogenous CCK seem not to influence milk intake while decrease pancreatic trypsin/protein ratio. However, endogenous CCK inhibit gastric emptying. The plasma CCK level was elevated due to the applied CCK-8 and camostate during the observed suckling period.
Gastrointestinal hormones appear to be important modulators of bile flow and composition. Insulin and glucagon induce choleresis at physiologic levels and may alter lipid output and concentration as well. The effects of many hormones such as insulin, glucagon, secretin, and pancreatic polypeptide are at least partially independent of their effects on neurovascular factors. Furthermore, recently studied hormones such as somatostatin, vasoactive intestinal polypeptide, and pancreatic polypeptide have also been shown not only to alter bile flow but to affect bile composition. Understanding the role of gastrointestinal hormones in hepatic physiology may elucidate the causes of gallstone formation, disorders of biliary excretion, and hypercholesteremic states.
Fourteen hormone-producing gastrointestinal tract tumors were tested for their content of somatostatin (SRIH) receptors, using receptor autoradiography and in vitro binding assay with tumor homogenates. All four gastrinomas tested had high levels of SRIH receptors, as did two of five insulinomas and four of five vasoactive intestinal peptide-producing tumors. Receptor visualization was obtained with two different radioligands, either a SRIH-28 analog, [125I]-[Leu8,D-Trp22,Tyr25]SRIH-28, or a SRIH octapeptide, the [125I]Tyr3 derivative of SMS 201-995 [H-DPhe-Cys-Phe-DTrp-Lys-Thr-Cys-Thr(ol)], [125I]204-090. In both cases receptors were localized over the tumor cell area only. Biochemical and pharmacological analyses of one insulinoma and two vipomas revealed saturable, high affinity binding sites with pharmacological specificity for SRIH. However, differences in receptor affinity of selected SRIH analogs, in particular SRIH-28 and SRIH octapeptides, were found between the insulinomas and the two other tumor types, vipoma and gastrinoma. The presence of SRIH receptors on various hormone-producing gastrointestinal tumors suggests that at least part of the beneficial effects of chronic therapy with SRIH analogs may be mediated through such membrane-bound receptors located on the tumor itself. SRIH receptor measurement may be of prognostic value in assessment of the therapeutic efficacy of SRIH analogs. They may also be of diagnostic value, if used as in vivo markers for the localization of small hormone-producing gastrointestinal tumors or their metastases.
When isolated rat liver cells were incubated for 15 min in the presence of vasoactive intestinal peptide, gastric inhibitory polypeptide, secretin or glucagon at a concentration of 2.0 micrograms/ml, glycogenolysis was stimulated by 30%-67% above the control. Slight but significant increase on gluconeogenesis was also observed by the addition vasoactive intestinal peptide, gastric inhibitory polypeptide or secretin. Somatostatin inhibited both glycogenolysis and gluconeogenesis induced by these hormones, but the degrees of inhibition are clearly much higher in the hormone-induced gluconeogenesis than glycogenolysis, and no significant inhibition of glycogenolysis was observed in case of glucagon and VIP. These results suggest the possibility that the so-called enterohepatic axis may play a part of roles in the regulation of serum glucose levels through gastrointestinal hormones belonging to the secretin family, and that it may be further regulated by somatostatin through gluconeogenesis.
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The value of ultrasonic scanning in the localization of hormone producing gastrointestinal tumours was assessed in 16 patients. Fifteen patients had Zollinger-Ellison syndrome and one patient had a VIP tumour. In four patients with Zollinger-Ellison syndrome ultrasonic scanning demonstrated a solid mass lesion of the head of the pancreas of 2.2.4 and 8 cm respectively. One of these diagnoses was verified by autopsy, one was also found by subsequent CT-scanning and angiography. In one patient ultrasonic scanning demonstrated a 3 cm tumour of the tail of the pancreas. At ultrasonically guided percutaneous fine needle biopsy tumour cells were aspirated. Biochemistry confirmed a VIP tumour. In 11 patients ultrasonic scanning was normal. By laparotomy in nine of these tumours of 1--3 cm were found in three patients 5.9 and 15 months after scanning and in two patients multiple 0.5 cm tumours within the duodenal wall were demonstrated one half and 9 months after ultrasound. In four patients tumours were not demonstrated by surgery. Two of the 11 patients were not operated upon, and the tumours have not been localized. The advantages of the complete atraumatic, rapid and relatively cheap ultrasound technique and the ability of an ultrasonically guided biopsy for the demonstration of malignancy justify ultrasonic scanning to be an initial method of investigation in the localization of hormone producing gastrointestinal tumours.
The present state of chemistry, structure-activity relationship and cellular mode of action of gastrointestinal polypeptide hormones (gastrin, secretin, cholecystokinin-pancreozymin, caerulein and bombesin) are reviewed. Possible structure of polypeptide receptors and the mechanism of peptide--receptor interaction are described, and the role of acetylcholine and histamine in secretion discussed. The present data support the hormonal-receptor significance of cyclic nucleotides (cAMP, cGMP) in the cellular regulation of secretion.
Gastrointestinal hormones were the subject of a review at The Royal Australasian College of Physicians meeting in 1973. Over the past nine years there has been such an explosion of knowledge about these peptides that even the experts in the field cannot keep up with the almost monthly discovery of either new peptides or new actions for old peptides. This paper will consider only four aspects of gastrointestinal hormones encompassing areas that are relatively new and reviewing the clinical usefulness of gastrointestinal hormones in practice. The areas which require consideration are: (i) How do we define a gastrointestinal hormone. (ii) Concept of brain-gut peptides and relationship of amphibian peptides to mammalian hormones. (iii) Of the plethora of peptides discovered, which have a defined role in normal physiology. (iv) When should a clinician ask for a gastrointestinal hormone estimate in clinical practice.
Gastrointestinal hormones and regulatory peptides of the gastrointestinal tract (GIT) influence many digestive functions and therefore it is essential in diseases of the GIT to search also for changes of GIT hormones in plasma or for an altered response of the target organ to hormonal abnormalities. An unequivocal physiological function is known so far only in gastrin, cholecystokinin, secretin, gastric inhibitory polypeptide, vasoactive intestinal polypeptide, motilin, somatostatin, glucagon and pancreatic polypeptide. The authors analyzes therefore different nosological unites, or clinical syndromes associated with excessive production of gastrin, vasoactive intestinal polypeptide, glucagon and somatostatin. He discusses also the syndrome of malignant carcinoid caused by excessive formation of serotonin in the enterochromaffin cells of the GIT which by its symptoms can imitate some apudomas of the GIT.
The author made a review about the origin, the biochemistry the physiological and pathological roles of gastrointestinal peptide hormones. They originate from the APUD cell system, chemically from the ancient growth hormone, or placental lactogen. The theoretical prosecgastrin's first sequencies form the "secretin family", the tail sequencies form the "gastrin family". The author describes many details of their effects on the different gastrointestinal organs, they behave mainly antagonistic way to each other. Finally a discussions is given about their role in the development of peptic ulcer, in the WDHA syndrome and in malabsorption.
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.
BACKGROUND/AIMS: Vasoactive intestinal contractor (VIC), an endothelinlike peptide and a putative gastrointestinal hormone, contracts gastrointestinal smooth muscle. The aim was to study VIC in relation to esophageal function. METHODS: Intramural nerves in opossum esophageal smooth muscle strips were stimulated in the presence of various concentrations of VIC and were stained for VIC immunoreactivity. RESULTS: VIC caused an atropine-resistant increase in the amplitude of nerve-induced contractions of the circular muscle. VIC alone contracted longitudinal muscle, and this effect was nearly eliminated by 1 mmol/L atropine. VIC caused an atropine-resistant increase in the resting tone of the lower esophageal sphincter muscle, but it did not affect nerve-induced relaxation of that muscle. VIC-immunoreactive nerve fibers occurred in the longitudinal muscle layer, in the muscularis mucosae, and around the ducts of esophageal glands. A few such fibers were found in the circular muscle layer. Nerve fibers and cell bodies of the myenteric plexus showed VIC immunoreactivity. In the stomach, immunoreactive nerve fibers occurred in muscularis mucosae and circular muscle but not in longitudinal muscle. CONCLUSIONS: VIC is localized in neuronal elements of the opossum esophagus and excites contractions in esophageal smooth muscle.
The objective of the present study was to measure plasma concentrations of the gastrointestinal hormones gastrin, somatostatin and cholecystokinin in plasma of children with recurrent abdominal pain, since these hormones affect gastrointestinal function. Forty-four children (7-16 years old) with recurrent abdominal pain and 36 control children (matched for age and sex) participated in the study. In a blood sample collected after an overnight fast, gastrin, somatostatin and cholecystokinin concentrations were measured by radioimmunoassay. The children with recurrent abdominal pain had higher plasma cholecystokinin levels (p < 0.001) than the controls. Whether or not this aberration is related to the clinical symptoms of children with recurrent abdominal pain remains to be established.