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PubMed1976

Isolation and evolution of the gastrointestinal hormones.

The history of the discovery of gastrointestinal hormones and the modern methods of their isolation are discussed in the first chapter. The origin of structural relationships of gastrointestinal hormones and the possible ways of evolution are analyzed in the second chapter. The methods used for isolation and identification of secretin and cholecystokinin are dealt with in detail; the isolation of vasoactive intestinal peptide, gastrin, "gastric inhibitory peptide" and enteroglucagon is discussed but briefly in the first chapter. The second chapter is of speculative character. It deals with the structural resemblances between gastrin-type (gastrin, cholecystokinin-pancreozyzimin, caerulein) and secretin-type (secretin, vasoactive intestinal peptide, glucagon, "gastric inhibitory peptide") hormones. The resemblances are explained by different evolutionary mechanisms.

Amino Acid Sequence↗
PubMed1977

Effects of gastrointestinal hormones on the electrical and mechanical activity of the cat stomach.

Effects of gastrointestinal hormones on electrical and mechanical activity of smooth muscle of cat stomach were studied. Spontaneous electrical activity of the antrum preparation consisted of slow waves with superimposed spike-like potentials. Phasic contractions occurred synchronously with the electrical activity. Pentagastrin, tetragastrin, pancreozymin and secretin increased frequency of slow wave component and amplitude of phasic contraction. Atropine and tetrodotoxin did not block the spike-like potential and slow wave component. Noradrenaline and verapamil blocked the phasic contraction. The excitatory effects of these gastrointestinal hormones were observed in the presence of atropine, tetrodotoxin and dibenamine, but not in verapamil. When the mechanical activity of the antral strips was depressed by caffeine or theophylline, the excitatory effects of gastrointestinal hormones were also suppressed. The excitatory effects produced by these hormones were potentiated by imidazole. These results suggest that gastrointestinal hormones have a direct excitatory action on the longitudinal smooth muscle of the antrum region and that the excitatory action is associated with phosphodiesterase activity and intracellular cyclic AMP content.

Action Potentials↗
PubMed1979

Clinical implications of the gastrointestinal hormones.

The importance of the gastrointestinal hormones to the clinician is considered under three headings: in disease states, diagnostic applications and therapeutic implications. Pearse's APUD (Amine Precursor Uptake and Decarboxylation) theory is referred to, and single and multiple endocrinopathies are discussed with particular referrence to diagnostic criteria and principles of management. The field of gastrointestinal endocrinology is rapidly developing and these peptides will assume an even greater importance to the clinician who must keep abreast with these developments.

Endoscopy↗
PubMed1990

Gastrointestinal hormones: from basic science to a clinical perspective.

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)

Gastrointestinal Hormones↗
PubMed1977

[New views on gastrointestinal hormones].

In addition to established gastrointestinal hormones--secretin, cholecystokinin-pancreozymin (CCK-PZ), gastrin, and glucagon---some 30 polypeptides with gastrointestinal actions can be listed. New aspects of these substances include the following: Gastrin and vasoactive intestinal peptide (VIP) can be also encountered in the central nervous system and may act as transmitters. CCK-PZ-serum concentrations are found markedly elevated in patients with exocrine pancreatic insufficiency; this may provide the opportunity to establish a realtively simple screening test. Moreover, there is evidence that serum-CCK-PZ levels serve as satiety signal. Secretin secretion is said to be enhanced in hunger and then to act as a lipolytic hormone. In addition to enteroglucagon, a gastrintestinal peptide identical to pancreatic glucagon has been detected. Gastric inhibitory polypeptide (GIP) inhibits gastric secretion and motility (enterogastrone activity) and together with glucose it stimulates insulin release (incretin activity). Motilin increases lower esophageal sphincter pressure, enhances gastric pepsin secretion and slows down gastric evacuation. Serum levels of pancreatic polypeptide may be found elevated as a diagnostic index in patients with endocrine peptide tumors of the pancreas. Recently, the potential importance of local (paracrine) actions of gastrointestinal polypeptides has been amphasized. Predominantly paracrine activity is exhibited by some prototype hormones, e.g. somatostatin, substance P, bombesian, and the non-polypeptide compounds, prostaglandins.

Bombesin↗
PubMed2006

Gastrointestinal hormones regulating appetite.

The role of gastrointestinal hormones in the regulation of appetite is reviewed. The gastrointestinal tract is the largest endocrine organ in the body. Gut hormones function to optimize the process of digestion and absorption of nutrients by the gut. In this capacity, their local effects on gastrointestinal motility and secretion have been well characterized. By altering the rate at which nutrients are delivered to compartments of the alimentary canal, the control of food intake arguably constitutes another point at which intervention may promote efficient digestion and nutrient uptake. In recent decades, gut hormones have come to occupy a central place in the complex neuroendocrine interactions that underlie the regulation of energy balance. Many gut peptides have been shown to influence energy intake. The most well studied in this regard are cholecystokinin (CCK), pancreatic polypeptide, peptide YY, glucagon-like peptide-1 (GLP-1), oxyntomodulin and ghrelin. With the exception of ghrelin, these hormones act to increase satiety and decrease food intake. The mechanisms by which gut hormones modify feeding are the subject of ongoing investigation. Local effects such as the inhibition of gastric emptying might contribute to the decrease in energy intake. Activation of mechanoreceptors as a result of gastric distension may inhibit further food intake via neural reflex arcs. Circulating gut hormones have also been shown to act directly on neurons in hypothalamic and brainstem centres of appetite control. The median eminence and area postrema are characterized by a deficiency of the blood-brain barrier. Some investigators argue that this renders neighbouring structures, such as the arcuate nucleus of the hypothalamus and the nucleus of the tractus solitarius in the brainstem, susceptible to influence by circulating factors. Extensive reciprocal connections exist between these areas and the hypothalamic paraventricular nucleus and other energy-regulating centres of the central nervous system. In this way, hormonal signals from the gut may be translated into the subjective sensation of satiety. Moreover, the importance of the brain-gut axis in the control of food intake is reflected in the dual role exhibited by many gut peptides as both hormones and neurotransmitters. Peptides such as CCK and GLP-1 are expressed in neurons projecting both into and out of areas of the central nervous system critical to energy balance. The global increase in the incidence of obesity and the associated burden of morbidity has imparted greater urgency to understanding the processes of appetite control. Appetite regulation offers an integrated model of a brain-gut axis comprising both endocrine and neurological systems. As physiological mediators of satiety, gut hormones offer an attractive therapeutic target in the treatment of obesity.

Appetite Regulation↗
PubMed1988

Effects of the pathway of bile flow on the digestion of fat and the release of gastrointestinal hormones.

The effects of an altered pathway of bile flow upon fat metabolism and gastrointestinal hormone release were investigated in patients undergoing biliary reconstruction procedures or external biliary drainage. After ingestion of a fat-enriched meal, patients with jejunal interposition hepaticoduodenostomy showed the same patterns as controls, with similar levels of plasma triglyceride and gastrointestinal hormones. On the other hand, patients with Roux-Y hepaticojejunostomy or external biliary drainage revealed the impairment of fat metabolism, although the response patterns were different. As for the changes in gastrointestinal hormones in the two groups, both gastric inhibitory polypeptide (GIP) and insulin levels were reduced, whereas glucagon-like immunoreactivity (GLI) levels rose, especially in the external biliary drainage group. It is considered that the disturbance of fat metabolism, in cases of internal or external biliary diversion, is closely related to change in GIP, insulin, and GLI release, in addition to the impairment of mixed micelle formation by bile and of hydrolysis by pancreatic enzymes.

Adolescent↗
PubMed1997

Gastrointestinal hormone in dumping syndrome and reflux esophagitis after gastric surgery.

Several problems are associated with gastric resection, including the dumping syndrome, reflux esophagitis, and malabsorption. A better understanding of the pathophysiological changes will shed light on new and improved therapy. Serum levels of seven circulating gastrointestinal hormones following a standardized solid meal and a brief score of symptoms were evaluated in 10 patients after partial distal gastrectomy and 12 patients after total gastrectomy, both groups reconstructed by Billroth II anastomosis, and 9 age-matched healthy controls. Patients underwent resection for gastric cancer and were studied 45 +/- 10 months after surgery. At the time of study, the patients had adapted well to surgery and no longer exhibited the severe symptoms of dumping seen immediately post-operatively. In contrast, the total gastrectomy patients exhibited the symptoms of reflux esophagitis. The gastrointestinal hormone changes could be divided into three patterns; obtunded responses (gastrin, PP), normal release (motilin, GIP) and increased secretion (CCK, neurotensin, PYY). In these, the early reaction of neurotensin correlated with the scores of late dumping syndrome and reflux esophagitis. In the literature, many gastrointestinal hormones have been shown to respond as an enhancement rather than adaptation. In other gastrointestinal hormones, secretin belonged to the obtunded type and enteroglucagon were classified in the increased type. However, pathophysiological significance of these hormonal changes remained uncertain. The late adaptive changes in gastrointestinal hormone secretion may help to compensate for loss of gastric motor function which accompanies gastric resection. On the other hand, these hormonal changes may exacerbate the esophageal reflux following gastrectomy.

Adaptation, Physiological↗
PubMed1978

The coordination of gastrointestinal hormones and the autonomic nerves.

We have conducted investigations on the relationship between gastrointestinal hormones and the autonomic nervous system. In this paper are described main themes of our investigations where a close association between gastrointestinal hormones and the autonomic nervous system was shown from the functional and morphological points of view. The "nervism" proposed by Pavlov, where the regulation of various organs in the body was thought to be accomplished wholly by the nervous system, was based on the findings on the physiology of the digestive glands. In the meantime, the discovery of secretin from the duodenal mucosa led Bayliss and Starling to propose a chemical co-ordination or a humoral regulatory mechanism in addition to the nervous system for the regulation of the various organs in the body. It is indeed surprising that the principle of two major regulatory mechanisms in the body was thus developed originally on the basic studies of the exocrine and endocrine function of the digestive system. Our investigations reported in this paper disclosed the fact that the neural and humoral regulatory mechanisms for gastrointestinal secretions acted not separately but in close association both morphologically and functionally.

Abdomen↗
PubMed1992

Characterization of functional receptors for gastrointestinal hormones on human colon cancer cells.

Studies demonstrate that some colon cancers possess receptors for various gastrointestinal hormones or neurotransmitters, the occupation of which can affect growth. These results are limited because frequently only a small number of tumors are studied, only 1 or 2 receptors are sought, and the effect on cell function is not investigated. In the present study, 10 recently characterized human colon cancer cell lines were studied to determine whether they possess receptors for any of 12 different gastrointestinal hormones or neurotransmitters and to determine whether these receptors mediate changes in cellular function. Each of the cell lines exhibited receptors for at least one radioligand. Receptors for vasoactive intestinal peptide (VIP) and muscarinic cholinergic agents occurred on 60%, bombesin and gastrin on 30%, beta-adrenergic agents and gastrin-releasing peptide (GRP) on 20%, and somatostatin, opiates, neuromedin B, and substance P on 10%. Analysis of [3H]N-methylscopolamine binding revealed a Kd of 0.2 nM for N-methylscopolamine with a binding capacity of 2500 sites/cell. With the agonist carbamylcholine, the receptor exhibited 2 classes of binding sites: one of high affinity (Kd 55 microM) representing 75% of the binding sites and one of low affinity (Kd 0.3 mM) representing 25% of the binding sites. Analysis of 125I-[Tyr4]bombesin binding revealed a receptor of high affinity (Kd 2.1 microM) with a binding capacity of 3300 sites/cell. Inhibition of binding by agonists revealed relative potencies of 125I-[Tyr4]bombesin greater than GRP much greater than neuromedin B, and two recently described antagonists were similar in potency to GRP. Analysis of 125I-VIP binding revealed a receptor having 2 classes of binding sites: one of high affinity (Kd 3.6 nM) and one of low affinity (Kd 1.7 microM) which represented the majority of the 5.5 x 10(6) binding sites/cell. The relative potencies of agonists were VIP greater than helodermin greater than peptide histidine methionine greater than secretin. Evaluation of biological activity mediated by the muscarinic cholinergic and bombesin receptors revealed an increase of intracellular calcium and of inositol triphosphate by specific receptor agonists. The presence or absence of receptors detected by binding correlated closely with the ability of selective receptor agonists to alter cell function. These results demonstrate the presence of several different receptors for gastrointestinal hormones or neurotransmitters, some described for the first time, on human colon cancer cell lines, including bombesin-related peptides, VIP, somatostatin, substance P, beta-adrenergic agents, calcitonin gene-related peptide, gastrin, muscarinic cholinergic agents, and opiates.(ABSTRACT TRUNCATED AT 400 WORDS)

Bombesin↗
PubMed2005

Gastrointestinal hormone abnormalities and G and D cells in functional dyspepsia patients with gastric dysmotility.

AIM: To investigate the relationship between gastric dysmotility, gastrointestinal hormone abnormalities, and neuroendocrine cells in gastrointestinal mucosa in patients with functional dyspepsia (FD). METHODS: Gastric emptying was assessed with solid radiopaque markers in 54 FD patients, and the patients were divided into two groups according to the results, one with delayed gastric emptying and the other with normal gastric emptying. Seventeen healthy volunteers acted as normal controls. Fasting and postprandial plasma levels and gastroduodenal mucosal levels of gastrointestinal hormones gastrin, somatostatin (SS) and neurotensin (NT) were measured by radioimmunoassay in all the subjects. G cells (gastrin-producing cells) and D cells (SS-producing cells) in gastric antral mucosa were immunostained with rabbit anti-gastrin polyclonal antibody and rabbit anti-SS polyclonal antibody, respectively, and analyzed quantitatively by computerized image analysis. RESULTS: The postprandial plasma gastrin levels, the fasting and postprandial plasma levels and the gastric and duodenal mucosal levels of NT were significantly higher in the FD patients with delayed gastric emptying than in those with normal gastric emptying and normal controls. The number and gray value of G and D cells and the G cell/D cell number ratio did not differ significantly between normal controls and the FD patients with or without delayed gastric emptying. CONCLUSION: Our findings suggest that the abnormalities of gastrin and NT may play a role in the pathophysiology of gastric dysmotility in FD patients, and the abnormality of postprandial plasma gastrin levels in FD patients with delayed gastric emptying is not related to the changes both in the number and gray value of G cells and in the G cell/D cell number ratio in gastric antral mucosa.

Adult↗
PubMedDate not supplied

[Gastrointestinal hormones in the blood serum of patients with chronic renal failure].

Content of gastrointestinal hormones (gastrin, insulin, glucagon, C-peptide), beta2-microglobulin, glomerular filtration rate (GFR) were studied in 65 patients with nephrolithiasis (NL) and in 73 patients with chronic renal failure (CRF). It was found that NL with GFR under 80 ml/min runs with elevated insulin, glucagon and C-peptide while CRF with CRF under 30 ml/min is characterized by aggravated disorders of hormonal homeostasis (gastrin, insulin, glucagons, C-peptide elevation). As gastrointestinal hormones in patients with CRF are high, it is recommended to combine medication with diet containing low amount of carbohydrates easy for digestion which is important in the treatment of CRF.

Adult↗
PubMed1998

The new biology of gastrointestinal hormones.

The classic concept of gastrointestinal endocrinology is that of a few peptides released to the circulation from endocrine cells, which are interspersed among other mucosal cells in the upper gastrointestinal tract. Today more than 30 peptide hormone genes are known to be expressed throughout the digestive tract, which makes the gut the largest endocrine organ in the body. Moreover, development in cell and molecular biology now makes it feasible to describe a new biology for gastrointestinal hormones based on five characteristics. 1) The structural homology groups the hormones into families, each of which is assumed to originate from a common ancestral gene. 2) The individual hormone gene is often expressed in multiple bioactive peptides due to tandem genes encoding different hormonal peptides, alternative splicing of the primary transcript, or differentiated processing of the primary translation product. By these mechanisms, more than 100 different hormonally active peptides are produced in the gastrointestinal tract. 3) In addition, gut hormone genes are widely expressed, also outside the gut. Some are expressed only in neuroendocrine cells, whereas others are expressed in a multitude of different cells, including cancer cells. 4) The different cell types often express different products of the same gene, "cell-specific expression." 5) Finally, gastrointestinal hormone-producing cells release the peptides in different ways, so the same peptide may act as an acute blood-borne hormone, as a local growth factor, as a neurotransmitter, and as a fertility factor. The new biology suggests that gastrointestinal hormones should be conceived as intercellular messengers of general physiological impact rather than as local regulators of the upper digestive tract.

Alternative Splicing↗
PubMedDate not supplied

The effect of gastrointestinal hormones on bile flow, bile lipid composition, and lithogenicity in rats.

The contribution of major gastrointestinal hormones to bile secretion was studied in 35 male Wistar rats with biliary, duodenal, and vena cava cannulae. Intravenous infusion of secretin, pancreozymin, and glucagon increased bile flow but only secretin affected bile lipid output. OP-CCK exerted the weakest choleretic effect. None of the hormones significantly changed the lithogenic index. Thus, gastrointestinal hormones could play an important role in the regulation of bile flow and bile lipid secretion in rats.

Animals↗
PubMed1978

[The significance of gastrointestinal hormones in gastroenterological practice].

In medical practice, diagnostic and therapeutic aspects of gastrointestinal hormones attract interest. Gastrin--in the form of pentagastrin--can be used for gastric secretory analysis and, in the analysis of exocrine pancreatic function, secretin and cholecystokinin-pancreozymin can be employed as stimulants. Diagnosis of hormone-producing tumors is possible by radioimmunological determination of serum levels of the hormone in question: so, dramatically high gastrin levels can be found in the Zollinger-Ellison syndrome while in the Verner-Morrison syndrome, VIP (vasoactive intestinal peptide) values are significantly elevated.--The therapeutic use of gastrointestinal hormones (gastrin, secretin) is waiting in the wings.

Cholecystokinin↗
PubMedDate not supplied

[Gastrointestinal hormones during minimal enteral feeding of sick premature infants].

OBJECTIVE: To measure gastrointestinal hormonal response (GHR) with minimal enteral feeding (MEF) in sick premature infants. METHODS: Forty-one babies birth weight < 1800 g receiving total parenteral nutrition or intravenous solutions entered the study. They were distributed in two groups: group I: 26 infants (early enteral feeding < or = 5 d) and group II = 15 infants (late enteral feeding = 10-14 d). A diluted special formula was used as MEF starting with 1 mL hourly with daily increments of 1 mL up to 120 mL. Basal and final determinations of GHR were done before and after the MEF. RESULTS: Both groups were similar in birth weight, postnatal age, and trophism. There were intragroup differences between basal and final GHR for all hormones in both groups. Subgroups by gestational age (< or = 32 vs > 32 weeks) and trophism (< or = 1250 vs > 1250 g) also showed basal-final differences. There were no complications related to the MEF. CONCLUSIONS: MEF favors secretion of gastrointestinal hormones in sick premature infants. Early MEF seems to be preferable to late one since it allows a faster secretion related to volume of the formula. MEF did not increase abdominal complications in our infants.

Birth Weight↗
PubMed1985

Effects of gastrointestinal hormones and their related compounds on gastric motility in the rat.

We examined the effects of certain gastrointestinal hormones on gastric motility using rat stomach preparatios in vivo. Changes of water level caused by the movement of the stomach which was filled with saline were recorded. Single injections of cholecystokinin (1, 2 and 4 micrograms/kg) induced relaxation of the stomach. Single injections of bombesin in low doses (below 0.2 microgram/kg) induced relaxation and in high doses (over 0.2 micrograms/kg) contraction after brief relaxation. Single injections of neurotensin (1, 2, 4 and 8 micrograms/kg), somatostatin (5, 10 and 20 micrograms/kg) and substance P (1, 2, 4 and 8 micrograms/kg) induced relaxation followed by contraction, but their dose-response relations were obscure. Infusions of neurotensin (1, 5 and 25 micrograms/kg/h) and somatostatin (2.5 and 5 micrograms/kg/h) enhanced the stomach tension, whereas substance P (1, 5 and 25 micrograms/kg/h) reduced it. Single injections and infusions of neurotensin, somatostatin or substance P showed different effects on gastric motility. On the other hand, Met-enkephalin (1, 10 and 100 micrograms/kg) and porcine motilin (1, 10 and 100 micrograms/kg) did not affect gastric motility in our rat stomach preparations. These results suggest that some gastrointestinal hormones take part in stomach movements.

Animals↗