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PubMed2003

The enteric nervous system II: gastrointestinal functions.

The enteric nervous system is involved in most of the physiological and pathophysiological processes in the gastrointestinal tract. This Minireview is part two of three and describes the role of the enteric nervous system in gastrointestinal functions (motility, exocrine and endocrine secretions, blood flow, and immune processes) in health and some disease states. In this context, the functional importance of the enteric nervous system for food intake, the gall bladder, and pancreas will be addressed. In specific, dysmotility, diarrhoea, constipation, non-occlusive intestinal ischaemia (intestinal angina), inflammation, cholelithiasis, cholecystitis, postcholecystectomy syndrome, and pancreatitis can be treated with neuroactive pharmacological agents. For example, serotonin receptor type four agonists can be used for the treatment of constipation, while nitric oxide synthesis inhibitors can be employed for the treatment of intestinal angina.

Animals↗
PubMedDate not supplied

Novel C-terminally amidated opioid peptide in human phaeochromocytoma tumour.

As has often been observed in hypothalamic releasing factors and gastrointestinal hormones, the carboxy-terminal amide structure is a unique feature of peptides exhibiting hormonal or physiological activities. Although a variety of opioid peptides have hitherto been identified, such a C-terminal amidated species has never before been discovered in mammals. Here we present the first identification of a novel opioid octapeptide with a C-terminal amide structure, henceforth designated as 'adrenorphin', in human phaeochromocytoma tumour derived from adrenal medulla. The complete amino acid sequence of adrenorphin was determined by microsequencing and corresponds to the sequence of the first eight amino acids of peptide E which is derived from proenkephalin A. Adrenorphin has also been identified chromatographically in normal human and bovine adrenal medulla. Adrenorphin exhibits potent opioid activity in guinea pig ileum assay, suggesting a specialized physiological function.

Adrenal Gland Neoplasms↗
PubMed1998

Rate of gastric emptying is a determinant of postprandial hypotension in non-insulin-dependent diabetes mellitus.

1. Postprandial hypotension is now recognized as an important clinical problem, particularly in the elderly and in patients with autonomic dysfunction. The mechanisms responsible are poorly understood; however, impaired regulation of splanchnic blood flow and the release of gastrointestinal hormones appear to be important. The effect of gastric emptying on the magnitude of the postprandial fall in blood pressure has not been evaluated. 2. The aim of this study was to determine whether there is a relationship between changes in blood pressure and the rate of gastric emptying after ingestion of 75 g of glucose in patients with non-insulin-dependent diabetes mellitus (NIDDM) and both young and older normal subjects. Sixteen patients with recently diagnosed NIDDM, median age 57 (39-79) years, 10 'young' subjects with a median age of 23 (19-26) years and nine 'older' subjects, median age 48 (40-68) years, were measured simultaneously for gastric emptying of 75 g of glucose in 350 ml of water blood pressure and blood glucose concentrations, commencing at approximately 10.00 hours after an overnight fast. Measurements of blood pressure were made in the sitting position immediately before glucose ingestion and at 15 min intervals up to 180 min. 3. Gastric emptying of glucose was not significantly different between the three groups [50% emptying time (T50): 95 +/- 7.3 min in patients with NIDDM compared with 120 +/- 13.2 min in the 'young' group and 97 +/- 8.1 min in the 'older' group]. There was a significant fall in mean blood pressure after the glucose load in the patients with NIDDM (P < 0.0001) and the 'older' normal subjects (P < 0.05), but not the 'young' normal subjects. Postprandial hypotension (fall in systolic blood pressure > or = 20 mmHg) was evident in seven (44%) patients with NIDDM and three (33%) 'older' normal subjects. The area under the change in mean blood pressure curve was related significantly to the gastric emptying T50 (r = 0.67, P < 0.005) in the patients with NIDDM, but not in either control group. 4. In conclusion, in patients with recently diagnosed NIDDM the fall in blood pressure after an oral glucose load is (i) greater than in both young and older normal subjects and (ii) related to the rate of gastric emptying.

Adult↗
PubMed1999

Does jejunal feeding activate exocrine pancreatic secretion?

BACKGROUND: The upper small bowel is of pivotal importance for the stimulation of exocrine pancreatic secretion in response to a meal. We hypothesize that more distal delivery of nutrients into the small intestine will result in less activation of pancreatic secretion. MATERIALS AND METHODS: Eight healthy subjects (3 male, 5 female; age 23 +/- 1 years) participated in two experiments, performed in random order. Subjects were intubated with a 4-lumen tube. Duodenal outputs of pancreatic enzymes and bilirubin were measured by aspiration using a recovery marker. The distal opening was used for continuous administration of a mixed liquid meal and located at either the ligament of Treitz or 60 cm further distally. Gallbladder volume was measured and blood samples were drawn for determination of gastrointestinal hormones. The duration of each experiment was 4 h; with 1 h fasting and 3 h continuous administration of nutrients. RESULTS: During proximal jejunal feeding, pancreatic enzyme output increased significantly over basal levels. No significant increase over basal levels was observed during distal jejunal feeding. Bilirubin output and gallbladder contraction were significantly (P < 0.05) reduced during distal compared to proximal jejunal feeding. No significant differences were found in plasma levels of CCK, PYY and neurotensin between proximal and distal jejunal feeding. CONCLUSION: Continuous feeding in the distal jejunum does not stimulate exocrine pancreatic secretion but maintains gallbladder contraction, although to a lesser extent. These effects are not related to hormonal changes but probably reduced activation of the enteropancreatic reflexes.

Adult↗
PubMed1999

Effect of bombesin on esophageal motility in humans.

We have investigated the effect of bombesin on esophageal motility and explored the mechanism of action of bombesin. Eight healthy subjects were studied in random order during intravenous administration of (1) bombesin, (2) bombesin + vagal cholinergic receptor blockade with atropine and (3) bombesin + somatostatin. Lower esophageal sphincter pressure (LESP) and esophageal body motility were recorded continuously by Dent-sleeve manometry. Bombesin significantly (p < 0.01) increased LESP from 20 +/- 2 mmHg to 43 +/- 6 mmHg. Neither atropine nor somatostatin significantly reduced the bombesin-induced increases in LESP. Bombesin significantly (p<0.05) increased peristaltic wave amplitude (from 61 +/- 4 to 105 +/- 9 mmHg) and duration (from 2.9 +/- 0.2 to 4.8 +/- 0.3 s) in the mid and distal part of the esophagus. Neither atropine nor somatostatin significantly reduced the esophageal body motor response to bombesin. In conclusion (1) bombesin significantly increases LESP and affects esophageal body motility by increasing peristaltic wave amplitude and duration and (2) the effect of bombesin on esophageal motility is not dependent on vagal cholinergic mechanisms and is not mediated by the action of gastrointestinal hormones released by bombesin.

Adult↗
PubMed1997

Alpha coat protein COPA (HEP-COP): presence of an Alu repeat in cDNA and identity of the amino terminus to xenin.

We previously sequenced the 4333-nucleotide cDNA of the COPA (HEP-COP) gene which encodes the human homologue of the alpha-subunit of the coatomer protein complex, involved in intracellular protein transport. Within the 3' untranslated region at nucleotides 4049-4333 was observed an Alu repeat containing conserved A and B block elements, and showing high homology to the human Alu-Sx subfamily consensus sequence. Upstream of the Alu repeat were noted a TATA box, a CAAT motif and two activating transcription factor (ATF)-like binding sites, which represent putative regulatory elements directing Alu transcription. In addition, the 25 and 35 N-terminal amino acid residues of COPA and its bovine homologue were identical to xenin-25 and proxenin, respectively. Xenin-25 is a gastrointestinal hormone that stimulates exocrine pancreatic secretion. This peptide is related to xenopsin, neurotensin and neuromedin N which are bioactive peptides derived from larger precursors via proteolytic cleavage by cathepsin E at processing sites determined by conserved C-terminal sequences, i.e. proline/valine-X-X-hydrophobic amino acid. Given the conformity of the C-terminal residues of xenin-25 (PWIL) and of its progenitor molecule, proxenin (VIQL), it is proposed that these peptides are generated by a similar mechanism of post-translational modification involving a parent precursor represented by the alpha-subunit of coatomer.

Base Sequence↗
PubMed2000

Peptide YY stimulates the expression of apolipoprotein A-IV gene in Caco-2 intestinal cells.

The effect of peptide YY, a gastrointestinal hormone, on the expression of the apolipoprotein A-IV gene in the intestinal epithelial cell line Caco-2 was examined by semiquantitative RT-PCR followed by Southern hybridization with an inner oligonucleotide probe. Apolipoprotein A-IV mRNA levels were increased in response to peptide YY in a dose- and time-dependent fashion. Western blotting revealed that the exogenous peptide YY increased the intracellular concentration of apolipoprotein A-IV. In contrast, apolipoprotein A-I, B, and C-III mRNA did not respond to peptide YY. Differentiated Caco-2 cells expressed Y1- but not Y2- and Y5-receptor subtype mRNA. The present results suggest that peptide YY modulates apolipoprotein A-IV gene expression, likely via the Y1-receptor subtype in intestinal epithelial cells.

Apolipoproteins A↗
PubMed2004

[Paracrine actions of the stomach-derived leptin].

Leptin, a 16 kilodalton protein-encoded by the ob gene, is involved in the regulation of food intake, body composition, and energy expenditure through a central feedback mechanism. Initially thought to be adipocyte-specific, the ob gene, as well as the leptin receptor, has been found in a variety of other tissues. Relevant to this review, the leptin gene and its receptor have been identified in the stomach, intestine, liver, and pancreas. Recent data also suggest that gut leptin may act locally within the gastrointestinal tract to influence intestinal functions such as nutrient absorption and may have a physiopathological implication. This review emphasises the concept that leptin may be a new gastrointestinal hormone.

Animals↗
PubMed1991

Hepatic and portal-drained viscera balances of amino acids, insulin, glucagon and gastrin in the pig after ingestion of casein or rapeseed proteins.

Hepatic and intestinal balances of amino acids, insulin, glucagon and gastrin were studied in 6 non-anaesthetized Large White pigs (mean body weight 64 +/- 4.8 kg) after ingestion of casein or rapeseed proteins. The animals were fitted with permanent catheters in the portal vein, the brachiocephalic artery and the right hepatic vein. In addition, 2 electromagnetic flow probes were implanted, one around the portal vein and the other around the hepatic artery. After a preliminary adaptation to each diet the animals received at 1-wk intervals and according to a double latin square design, 3 test meals of 800 g each, one containing 23.2% of rapeseed concentrate (diet RA 12) and the others 13.9 or 27.8% of hydrochloric casein (diets CA 12 and CA 24). Each observation period lasted 12 h. Amino acids from all diets were very well absorbed. In 12 h, the absorption of total amino acids as a percentage of the ingested quantities was 99% for CA 12, 102% for CA 24 and 104% for RA 12. Hepatic uptake of total amino acids in 12 h expressed as a percentage of the absorbed quantities was 13% for CA 12, 66% for CA 24 and 25% for RA 12. Differences in the hepatic extraction rate of essential amino acids appeared between the 2 levels of casein ingestion and for Arg between the 2 protein sources. Whatever the nature of the ingested protein or the level of casein, the liver showed a net production of Asp and Glu. The production and hepatic balance of insulin were the lowest after ingestion of RA 12. No differences were noted in the same parameters for glucagon and gastrin. Independently of the nutritional situation, the hepatic extraction rate of insulin appeared to be higher than those of glucagon and gastrin. Our results showed that the nature as well as the level of dietary proteins have large effects on the sequence and volume of absorptive phenomena, the hepatic metabolism of nutrients, the production of gastrointestinal hormones and the non-hepatic tissue disposal of absorbed nutrients.

Absorption↗
PubMed1993

Post-prandial lipase, pepsin and acid secretion of a Heidenhain pouch in the rabbit.

The kinetics of the gastric secretion of lipase, pepsin and acid were studied after a meal in Heidenhain-pouch rabbits. After a 24-h fast, feeding immediately stimulated (< 15 min) lipase (x 4.1) and later on pepsin (x 1.8) output which reached respectively 16 and 47% of the output observed after pentagastrin stimulation (64 micrograms.kg-1.h-1 for 1 h), and which were significantly correlated. Lipase concentration was enhanced earlier and to a greater degree (x 7.3) than pepsin concentration (x 2.5). No stimulation of high basal acid secretion occurred. It was concluded that: 1) gastric lipase secretion is stimulated by feeding in the rabbit; 2) pepsin secretion is stimulated by feeding. The modalities of the secretion of lipase and pepsin are compatible with the existence of distinct secretory cells; 3) acid secretion is not stimulated by feeding. The decrease in acid secretion during the post-prandial phase favors a physiological role for lipase which is altered by low pH. The absence of acid stimulation by feeding in the rabbit, in contrast to other species, requires additional studies on the release of gastrointestinal hormones, namely gastrin, cholecystokinin and somatostatin.

Animals↗
PubMed1975

In vitro studies of calcitonin release in man.

The influence of various agents on calcitonin release from human thyroid was studied in vitro. Under the condition of this investigation, calcium, magnesium and phosphate did not stimulate calcitonin release from short-term incubated slices of human thyroid. However, pentagastrin and USP glucagon were potent stimulators of calcitonin release. Theophylline and dibutyryl cyclic AMP were also potent stimuli. A highly purified preparation of pancreatic glucagon was without an effect. Those agents which stimulated calcitonin release were associated with augmented cyclic AMP accumulation. Although maximal discharge of calcitonin required the presence of calcium, out in vitro experiments raise the question as to whether a gastrointestinal hormone, rather than calcium, might not be the principal agent affecting calcitonin release.

Bucladesine↗
PubMed1975

[The vaso-active intestinal polypeptide in Verner-Morrison syndrome].

A 40-year-old man with the Verner-Morrison syndrome (refractory watery diarrhoea and hypokalaemia in islet-cell tumour of the pancreas) had an islet-cell carcinoma of the non-B-cell type with metastases to liver and mesenteric lymph nodes. High concentrations of a vasoactive intestinal polypeptide (VIP) were demonstrated in tumour tissue and plasma by radioimmunological tests. After surgical removal of the tumour the plasma VIP concentration fell to normal. Immunohistochemical tests of the tumour for gastrointestinal hormones demonstrated marked fluorescence only for vaso-active intestinal polypeptide. It is assumed that this polypeptide is largely responsible for the clinical signs. In the described case the severe watery diarrhoea ceased after glucocorticoid administration.

Acute Kidney Injury↗
PubMed1997

Stimulative effects of saponin from kikyo-to, a Japanese herbal medicine, on pancreatic exocrine secretion of conscious rats.

Our previous report stated that kikyo-to, a Japanese herbal medicine, consisting of the roots of Platycodon grandiflorum and Glycyrrhiza sp., stimulates the pancreatic exocrine secretion of conscious rats. The present study focused on the effective components of kikyo-to and the mechanism of stimuli to pancreatic secretion of rats. When 10 to 100 mg of platycodin D, a saponin from the root of Platycodon grandiflorum, was intragastrically administered, the pancreatic secretion of rats was stimulated. At the same time, the plasma CCK concentration increased. On the other hand, the stimulative effects of glycyrrhizin, a saponin from the root of Glycyrrhiza sp. were weak compared to platycodin D. The effects of 10 mg/kg of platycodin D on pancreatic secretion were inhibited by loxiglumide (50 mg/kg, i.g.), a CCK receptor antagonist. In contrast, the suppressive effect of atropine (300 micrograms/kg/h, i.v.) on pancreatic secretion was reduced by administering 10 mg/kg of platycodin D. In addition, up to 1 mM of platycodin D did not inhibit the trypsin activities in vitro. In conclusion, kikyo-to serves to stimulate pancreatic exocrine secretion mainly because platycodin D causes gastrointestinal hormones, particularly, CCK to be released from the duodenum.

Animals↗
PubMed1989

The influence of the duodenal passage on postprandial neurotensin release in dogs.

All types of gastric resections induce an abnormal release of gastrointestinal hormones. The missing duodenal passage seems to be the most important factor for these disturbances. In the present study we have examined the effect of exclusion and restoration of the duodenal passage on the postprandial release of neurotensin in dogs. After feeding a standard canned dog meal, exclusion of the duodenal passage by a Billroth-II-resection caused a significant increase in postprandial neurotensin release compared to the control group (peak levels 52 +/- 5.6 to 29 +/- 6 pg/ml preoperatively, integrated output 2132 +/- 228 to 3604 +/- 213 pg/ml x 150 min. p less than 0.05). Reconstruction of the duodenal passage by the Biebl-Henly-Soupault-procedure tended the elevated neurotensin levels towards normal (peak levels 36 +/- 4.8 pg/ml, integrated output 2448 +/- 236 pg/ml x 150 min., p less than 0.05). From our data we conclude that changes in intestinal transit time are responsible for the pathological increase in neurotensin release after exclusion of the duodenal passage.

Animals↗
PubMed1988

Pharmacology of the sphincter of Oddi.

The sphincter of Oddi is the smooth muscle connection between the bile duct and the duodenum. Its physiological function is associated with a regular motility characterized by phasic contractions superimposed on the sphincter of Oddi baseline pressure. Recently introduced ERCP-manometry permits further studies of sphincter of Oddi pharmacology. A number of drugs have so far been studied. Sedatives of the diazepam type had no effect on the sphincter, while butylscopolaminium bromide, a typical neurotropic agent, brings about cessation of the sphincter motility for 3-8 minutes. Hymecromon lowered the sphincter baseline pressure from 9.8 to 7.8 mmHg. A 1.2 mg sublingual dose of nitroglycerin, a typical musculotropic agent, caused significant relaxation of the sphincter, and decreased baseline pressure from 8.9 mmHg to 2.9 mmHg; Sphincter motility was not affected. Morphine-like analgetics, in particular pentazocine, elevated sphincter baseline pressure, but buprenorphine and tramadol did not. Pharmacological doses of gastrointestinal hormones also affect the sphincter; CCK octapeptide, glucagon and secretin are able to decrease sphincter of Oddi baseline pressure, and CCK octapeptide abolishes sphincter motility. Sphincter of Oddi pharmacology is of clinical interest. The administration of sphincter-relaxing agents, in particular nitroglycerin and butylscopolaminium bromide, enables the endoscopist to extract small common bile duct stones without previous papillotomy. Analgetics that induce sphincter contraction and thus hinder the flow of bile and pancreatic juice, may be helpful for the treatment of pain in patients with pancreatico-biliary disease. Investigations into the effect of CCK on the healthy and diseased sphincter permit us to identify patients with sphincter dysfunction using a special CCK-provocation test.

Ampulla of Vater↗
PubMed1989

[Liver calcifications in metastasizing vipoma].

A 53-year-old woman had suffered from watery diarrhoea and substitution-requiring hypokalaemia for 18 months. Ultrasonography and abdominal x-ray revealed multiple calcifications in the liver. Retrograde cholangiopancreaticography, performed because an endocrine-secreting pancreatic tumour was suspected, demonstrated occlusion of the major pancreatic duct and calcification in the body of the pancreas. Gastrointestinal hormone levels were elevated (vasoactive intestinal polypeptide 950 pg/ml, pancreatic polypeptide 1000 pmol/l and neurotensin 86 pmol/l) in the blood, and immunohistochemical results on cells of an adenocarcinoma obtained by needle biopsy confirmed a metastasizing VIPoma. Administration of the somatostatin analogue SMS 201-995 achieved marked improvement.

Adenoma, Islet Cell↗