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Gastrin and cholecystokinin levels in rats fed soya bean trypsin inhibitor.

The effect of dietary soya bean trypsin inhibitor (SBTI) on rat pancreas, stomach, duodenum and two gastrointestinal hormones (gastrin and cholecystokinin (CCK] levels was investigated over a 21 day period. Rats were fed either a complete diet containing 17% protein as casein (control animals), or the same diet supplemented with 1.1% SBTI (test animals). After 21 days the weight of the pancreas in the test group was 90% higher than that in the controls. The stomach antrum, and duodenum showed no change. The gastrin content in the antrum in fasted rats increased after SBTI feeding whereas plasma gastrin levels remained the same. Dietary SBTI had no effect on fasting CCK levels either in duodenal mucosa or in plasma. The results obtained on gastrin values indicate that SBTI stimulates gastrin biosynthesis in the rat antrum but does not alter its release into the circulation. Results obtained on CCK values suggested the following hypothesis: the endocrine tissue of the duodenum, where CCK is synthesized and stored, represents a relatively large reservoir of this hormone. In addition the secretory capacity of this tissue is probably much higher then is required during normal physiological conditions. Therefore, this tissue does not undergo any adaptive changes after prolonged overstimulation by SBTI. The plasma CCK peak following SBTI intake is probably much higher than after control diet, but clearance of CCK from plasma is relatively fast. Consequently, the high levels of CCK after SBTI intake produce overstimulation of pancreatic secretion and in the long term alter the pancreatic function and morphology but return to normal levels in fasting state.

Animals↗

Ultrastructural and cytochemical studies on the cytodifferentiation of duodenal endocrine cells.

The development of cytodifferentiation of endocrine cells that produce the gastrointestinal hormones gastrin, cholecystokinin and secretin have been studied by a combined fluorescence-cytochemical, immunocytochemical and ultrastructural approach. The results show that, during development, several ultrastructurally distinct cell types exhibit COOH-terminal gastrin and cholecystokinin immunoreactivity. Furthermore, some cells simultaneously contain both gastrin- and cholecystokinin-specific antigenic determinants. Studies on the time course of development of gastrin and cholecystokinin cells, together with the above-mentioned data, suggest that gastrin cells may be converted into cholecystokinin cells in development. During this period, gastrin, cholecystokinin and secretin cells store the biogenic monoamine, 5-hydroxytryptamine a feature not displayed by the adult counter-parts of these cells. In the adult duodenum, characteristic enterochromaffin (EC) cells store 5-hydroxytryptamin for which, evidence for a possible hormonal role has been presented. Taken together, our data indicate that the differentiation of duodenal endocrine cells occurs in distinct steps, each involving a restriction in the biosynthetic repertoire of the cell.

Animals↗

Effect of cholecystokinin-pancreozymin (CCK-PZ) on glycoprotein secretion from mouse gallbladder epithelium: an ultrastructural and cytochemical study.

Structural changes in the gallbladder epithelial cells of the mouse were studied following in vivo and in vitro stimulation of the gallbladder with the gastrointestinal hormone cholecystokinin-pancreozymin (CCK-PZ). Signs of increased secretory activity were observed within the first 2-3 min after hormone administration. At the ultrastructural level, best visualized with the PA-CrA-silver technique, granule discharge was observed, as was an overall increase in size of the granules. After prolonged in vitro incubation or repeated in vivo stimulation, there was an almost total depletion of secretory granules. This phenomenon is accompanied by an enhanced uptake of extracellular thorium dioxide by endocytotic vesicles at the apical cell surface. An exocytosis-endocytosis coupling mechanism may be important for membrane conservation in the gallbladder epithelial cells. The findings establish that the hormone CCK-PZ stimulates the secretion of glycoproteins from the mouse gallbladder epithelium.

Animals↗

New types of islet cells in a cyclostome, Petromyzon marinus L.

Four types of acidophilic granular cells, in addition to B-cells, are identified in the islet organ of anadromous specimens of two subspecies of Petromyzon marinus by light and electron microscopy. Three of these acidophils (PI, PII and PIV-cells) occur in both the cranial and hepatic islets while a fourth type (PIII-cell) has only been found in the hepatic islet of some animals. The granules of the PI-cells stain with ponceau de xylidine, give a distinct tryptophan reaction and in ultrastructural examination show large, dense granules. The PII-cells contain unusual crystals and appear to be a non-secretory stage of the PI. The PIII-cells stain deep-red and acid fuchsin. They contain very large, dense granules and some lysosomes. PIV-cells stain selectively with phosphotungstic acid-hematoxylin and ultrastructurally, contain small, more or less dense granules. It appears that PI- and PIV-cells develop directly from B-cells, while the PIII-cells derive from PI-cells. despite their direct or indirect origin from B-cells, the PI-, PIII- and PIV-cells show characteristic features of functionally independent endocrine cells. Petromyzon marinus may be an ideal model for the understanding of phylogenetic and pathological interrelationships between islet and gastrointestinal hormones. It is clear that the interpretation of the islet organ of the cyclostomes, which has been generally considered a source of insulin only, requires a revaluation.

Animals↗

Neuronal cholecystokinin, gastrin-releasing peptide, neurotensin, and beta-endorphin in the intestine of the guinea pig. Distribution and possible motor functions.

The guinea-pig intestine was found to harbor nerve fibers containing immunoreactive cholecystokinin (CCK), gastrin-releasing peptide (GRP), neurotensin or beta-endorphin. Such fibers occurred in the myenteric and submucous ganglia and in the smooth muscle. GRP- and CCK-fibers, in addition, were found in the mucosa. Following colchicine treatment, neuronal perikarya in the myenteric ganglia displayed CCK-, GRP-, or beta-endorphin immunoreactivity. CCK-immunoreactive perikarya were located also in the submucous ganglia. Neurotensin-immunoreactive cell bodies could not be detected. The presence of immunoreactive neuronal perikarya in intramural ganglia indicates that CCK-, GRP- and beta-endorphin-containing fibers are intrinsic to the gut wall. GRP, neurotensin, and beta-endorphin were identified in extracts of smooth muscle by immuno-chemical and chromatographic analysis. CCK-8, GRP and neurotensin contracted the isolated taenia coli. Tetrodotoxin reduced the response to CCK-8 but not that to GRP and neurotensin, suggesting that the two latter peptides act directly on smooth muscle receptors. The effect of CCK-8 is partly mediated by cholinergic nerves, since not only tetrodotoxin but also atropine greatly reduced the CCK-8-induced contractile response. The substance P (SP) antagonist, (D-Pro2, D-Trp7,9)-SP1-11 had no effect on the CCK-8-induced contraction of the taenia. CCK-8 enhanced the SP-mediated (atropine-resistant) contractile response to electrical stimulation but not that mediated by acetylcholine. beta-Endorphin had no effect on the tension of the muscle but reduced the response to electrical stimulation (cholinergic as well as SP-mediated) through a naloxone-sensitive mechanism. While CCK-8 and beta-endorphin seem to play neuromodulatory roles in the taenia coli, the significance of GRP and neurotensin remains enigmatic.

Animals↗

Vapreotide, a new somatostatin analogue in the palliative management of obstructive ileus in advanced cancer.

Obstructive ileus is not common, but is a very distressing syndrome in a palliative care unit. The case of a 86-year-old woman with obstructive ileus due to advanced pancreatic cancer is presented. Successful management was made possible by a new somatostatin analogue (Vapreotide), administered i.m. at weekly intervals. Vapreotide was found to reduce nausea and vomiting considerably, by inhibiting the release and action of gastrointestinal hormones and the secretory and motor functions of stomach and intestines. The role of somatostatin analogues in the management of obstructive ileus in advanced cancer is discussed.

Aged↗

Peptide YY release after intraduodenal, intraileal, and intracolonic administration of nutrients in rats.

Peptide YY (PYY) release was studied by measuring radioimmunoassayable PYY in the arterial plasma of anaesthetized rats receiving into the duodenum, ileum or colon either a complete semi-liquid meal (3ml, 21kJ) or elemental nutrients as isocaloric or isoosmolar solutions. PYY release induced by the intraduodenal meal peaked at 60min and lasted more than 120min. The integrated response of PYY over 120min was larger when the meal was administered into the duodenum than into the ileum. The undigested meal induced no release of PYY over a 120-min period when administered into the colon. When injected into the duodenum in isocaloric amounts to the meal, glucose and amino acids led to the release of as much PYY as did the meal, whereas oleic acid led to the release of less PYY. Part of these responses were due to osmolarity, since administration of intraduodenal hyperosmolar saline led to the release of about half as much PYY as did hyperosmolar glucose. In moderate amounts, and injected as a solution isoosmolar to plasma, oleic acid was a major PYY releaser; the amounts released were at least two times larger when oleic acid was administered into the duodenum than into the ileum and colon. Isoosmolar glucose and amino acids led to the release of no PYY when injected into the duodenum, but were nearly as active as oleic acid in the colon. Short-chain fatty acids induced the release of PYY when injected into the colon, but not into the ileum. Hexamethonium suppressed PYY release induced by the intraduodenal meal, but did not change PYY release induced by glucose or oleic acid in the colon. Urethane anaesthesia did not reduce PYY release induced by the intraduodenal meal. These results suggest that two mechanisms at least contribute to PYY release in the rat. An indirect, neural mechanism, involving nicotinic synapses, is prominent in the proximal small intestine; the stimulation is transmitted to ileal and colonic L-cells by undetermined pathways, but contact of nutrients with L-cells is not needed. Another mechanism, probably direct and quantitatively smaller, occurs in the distal intestine when nutrients come into contact with the mucosa containing L-cells. Glucose, fatty acids and amino acids stimulate differentially the proximal and distal mechanisms.

Anesthesia↗

Effects of parenteral secretin--cholecystokinin and of duodenal acid perfusion on gastric secretion in duodenal ulcer patients.

The effect of parenteral secretin-cholecystokinin and duodenal acid perfusion on broth-stimulated gastric acid secretion was studied in 11 duodenal ulcer patients. Statistically significant inhibition occurred in both experimental conditions. The effect of secretin-cholecystokinin was more marked than the effect of duodenal acid perfusion. A poorly responsive subgroup of patients appeared to be responsible for the diminished inhibitory effect of duodenal acid perfusion. In this poorly responsive group there was a diminished duodenal volume response as well as diminished duodenal acid clearing. We conclude that there may exist a diminished release of gastrointestinal hormones such as secretin and cholecystokinin in certain duodenal ulcer patients.

Adult↗

Control of lower-esophageal-sphincter contractile activity by motilin in conscious dogs.

The effect of synthetic motilin on contractile activity in the lower esophageal sphincter (LES) and the stomach has been studied in 5 healthy dogs by means of chronically implanted strain gage force transducers. Motilin produced strong contractions in the LES and the stomach simultaneously after intravenous doses ranging from 0.3 to 2.7 microgram/kg hr, which were similar to the naturally occurring interdigestive contractions in the LES and the stomach. However, these contractions could be induced only in the interdigestive state; infusion of motilin into dogs in the digestive state brought about no significant effect on either the LES or the stomach. Motilin-induced contractions in the LES and the stomach were instantly abolished by ingestion of food. It is considered that the contractions induced by motilin are identical with the naturally occurring interdigestive contractions in the LES and these contractions are the most orad component of the interdigestive cyclic recurring caudad-moving bands of strong contractions in the dogs.

Animals↗

Absorption of different elemental diets in a short-bowel syndrome lasting 15 years.

In a patient with total colectomy and only 120 cm of the proximal small bowel remaining after resection for Crohn's disease, comparative studies were performed on the absorption of isocaloric amounts of Vivonex HN, Flexical, Codelid, Jejunal, and Precision LR. These elemental and/or complete diets were fed by a nasogastric tube at a constant rate of 260 ml/hr, 1 cal/ml, 2185-2660 ml per feeding period of 8.4-10.2 hr daily. Discharge of intestinal fluids from the jejunal stoma ranged between 2940 ml (Vivonex HN) to 4760 ml (Jejunal) per daily feeding period, resulting in a net intestinal loss of fluids and dehydration with the exception of Flexical. Jejunostomy discharge on Flexical was only 1325 ml per comparable period. The patient tolerated dietary fat relatively well absorbing 61% of 87 g of fat from Flexical and 60% of 108 g from a natural blenderized diet. The other diets used were either fat-free or with a minimum amount of fat. The second best tolerated diet was Vivonex HN, the feeding of which resulted in the highest intestinal retention of nitrogen (84% of the 16.3 g fed as opposed to 78% of 9.1 g fed in Flexical). Vivonex HN also had the highest intestinal retention of phosphorus. Intestinal fluid absorption was not related to the intestinal transit time measured by a nonabsorbable marker or to the osmolality of diets. Diets containing fat may inhibit secretion by the "enterogastrone-like" effect induced by dietary fat in the remaining bowel. High amino acid content of some of the low-fat diets may release gastrointestinal hormones which stimulate secretion, and the simple carbohydrates prevent fluid absorption. In the short-bowel syndrome with normal functions of the pancreaticobiliary system, diets based on fat and protein hydrolysate should be the nutritional therapy of choice.

Colectomy↗

Somatostatin inhibits motilin-induced interdigestive contractile activity in the dog.

The interaction between motilin and somatostatin on gastrointestinal motor activity was studied in fasted, unanesthetized dogs. Contractions of the stomach, duodenum, jejunum, and ileum were recorded with extraluminal strain gage force transducers. Motilin initiated a pattern of contractile activity which closely resembled phase III of the interdigestive motor complex. Somatostatin delayed the onset of the motilin response and reduced motor activity in the stomach and the jejunum. During somatstatin infusion the motilin-induced contractile pattern did not migrate to the jejunum. The cycle of natural interdigestive motor complexes was also interrupted by somatostatin. Somatostatin alters natural and motilin-induced interdigestive migrating motor complexes of the canine gastrointestinal tract.

Animals↗

Motilin regulation of canine interdigestive intestinal motility.

The objective was to determine whether motilin regulates cyclical interdigestive motility in the jejunum as well as in the duodenum. In four conscious dogs with an intact innervated duodenum, an autotransplanted (extrinsically denervated) 75-cm loop of proximal jejunum, and an autotransplanted, in situ distal jejunum, interdigestive myoelectrical complexes cycled independently in all three regions of small bowel. Plasma concentration of motilin was greater during phase III of the duodenal cycles (304 +/- 37 pg/ml) than during phase I (235 +/- 37 pg/ml) or phase II (235 +/- 39 pg/ml; P less than 0.05), but the concentration did not vary consistently with the phases of the cycles in the autotransplanted jejunal segments. Intravenous infusions of motilin (0.6 microgram/kg/min for 5 hr), begun 15-30 min after passage of phase III through the duodenum, shortened the interval between phase IIIs in the duodenum from 147 +/- 14 min before infusions to 44 +/- 3 min during the infusions (P less than 0.05), but did not alter consistently the interval between phase IIIs in the autotransplanted jejunal segments. Feeding decreased plasma motilin concentration. The data were consistent with motilin regulation of interdigestive motility in intact, innervated canine duodenum but not in extrinsically denervated jejunum.

Action Potentials↗

Complex clocks.

Periodic activity of the digestive tract is now a well-recognized phenomenon. Some years ago, it was proposed that this was controlled by a single "clock" at a distance from the gut, but subsequent study has shown that this explanation was inadequate. "Black box" analysis of available data suggests a new model which requires multiple clocks; this model is proposed as being consistent with current knowledge of the system.

Animals↗

Certain aspects of normal and abnormal motility of sphincter of Oddi.

Applications of electromyographic and endoscopic manometric techniques in experimental and clinical studies have enhanced our knowledge of the normal physiology and motility disturbances of the sphincter of Oddi. The sphincter of Oddi has an active role in coordinating the time and rate of secretion of biliopancreatic juice into the duodenum. In the opossum, the sphincter of Oddi exhibits spontaneous contractions that migrate distally along the sphincter and expels its contents into the duodenum. Although the motor activity of the sphincter of Oddi is independent from that of the duodenum, there is a correlation between the frequency of bursts of spike potentials in the sphincter of Oddi and the migrating motor complex phases in the duodenum. Abnormal motility of the sphincter of Oddi has been reported during endoscopic manometric evaluation of patients with choledocholithiasis and sphincter of Oddi dyskinesia. Patients with common bile duct stones have an increase in the frequency of retrograde propagation of phasic waves. Elevation of basal pressure as well as an increase in the frequency and amplitude of sphincter of Oddi phasic waves and the common bile duct-duodenum gradient pressure may occur in patients with sphincter of Oddi dyskinesia. Endoscopic manometric studies of the sphincter of Oddi may become an important method to diagnose sphincter of Oddi dyskinesia.

Ampulla of Vater↗