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PubMed1980

Fasting plasma motilin levels are related to the interdigestive motility complex.

Fluctuations of plasma motilin and gastrin levels were analyzed in relation to the interdigestive motor complex in humans, taking the onset of a duodenal activity front (phase 3 of the complex) as a reference point and the time lapse between two fronts as a time base. Statistical analysis showed a close relation between motilin fluctuations and the occurrence of duodenal activity fronts.

Duodenum↗
PubMed1980

[Physiology and pathophysiology of bile secretion].

After introductory anatomical considerations a survey is given of the composition of bile and the physiology of bile secretion. According to the modern conception the bile acids give the osmotic power for the excretion of water and electrolytes. Apart from this, a bile fraction, which is also secreted by the liver cells into the canaliculi, is present, and in the biliary ducts a further volume fraction independent of bile acid is added, the secretion of which is determined by gastrointestinal hormones. Processes of reabsorption play a role particularly in the gallbladder. By formation of micelles the bile salts render the excretion of cholesterol possible. A normal bile secretion is necessary for the normal emulgation, digestion and absorption of the fats.

Bile↗
PubMedDate not supplied

[Postoperative enteral nutrition with a high content of mono- and polyunsaturated fatty acids].

We have done a clinical study in patients with benign biliary disease and indication for surgery, with the aim of analyzing some parameters of gastric secretion, biliary and pancreatic function, and gastrointestinal hormones in relation to the quantity and quality of the dietary fat (monounsaturated and polyunsaturated fatty acids), acting on the postoperative enteral ingestion, modifying the lipid source by its elaboration. In the present work we show the results derived from the analysis of the gastric and duodenal juices in relation to the type of fat administered, with a global description of the study being necessary. The studied sample consisted of 20 patients diagnosed with simple gallstones, who were divided into two groups (n = 10) according to the usual ingestion of fats: olive oil (Olive Group) or sunflower oil (Sunflower Group). A control group (n = 10) has also been considered, without taking into account their dietary habits. The patients were subjected to surgery, and after the immediate postoperative period they were fed, orally, with an enteral diet prepared with commercially available formulae (modular EDA); as a lipid source we have added olive oil, rich in monounsaturated fatty acids, for the Olive Group, and sunflower oil, rich in polyunsaturated oil, for the Sunflower Group. In the control group cream was added as lipid source (mono and polyunsaturated fatty acids). The caloric value of the diet is calculated based on the caloric value of its components (protein: 17%, carbohydrate: 53%, lipid 30%). The daily caloric requirements are determined based on the daily basal metabolism, according to the Harris-Benedick formula.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1995

Secretin, cholecystokinin and the biliary canalicular secretion in the rat.

An attempt has been made to further assess which fraction of bile can be stimulated by the main gastrointestinal hormones in rats. In the cannulated conscious animals the i.v. infusions of glucagon, impure Boots secretin, impure Boots cholecystokinin (CCK) and OP-CCK resulted in 8.9% (N.S.), 68.5% (P < 0.001), 88.7% (P < 0.001) and 19.0% (P < 0.05) increase in the estimated bile acid-dependent bile flow (BAF) and in 25.4% (P < 0.01), 49.2% (P < 0.001), 44.5% (P < 0.001) and 1.6% (N.S.) increase in the estimated bile acid-independent bile flow (BAIF), respectively as compared to the control values. When the calculated BAF values corresponding to the bile acid impurities in Boots secretin and Boots CCK were subtracted from BAF and BAIF values obtained during hormone infusions (the corrected values), the increase in both BAF and BAIF was equal to 38.9% (P < 0.02) and 29.4% (P < 0.02) during Boots secretin infusion and to 61.1% (P < 0.01) and 29.4% (P < 0.02) during Boots CCK infusion, respectively as compared to the control values. It can be suggested that the hormonal impurities in the Boots preparations interacting with the principal hormonal component are able to stimulate BAF in the rat. Further extensive study embracing the interactions of the purified gut hormones may confirm their role in the control of canalicular bile secretion in the rat.

Animals↗
PubMed1993

A role for cholecystokinin-stimulated protein tyrosine phosphorylation in regulated secretion by the pancreatic acinar cell.

Cholecystokinin (CCK) is a gastrointestinal hormone that acts through a G protein-coupled receptor to stimulate pancreatic enzyme secretion. In this work, we demonstrate that CCK stimulation of dispersed pancreatic acini results in increased tyrosine phosphorylation of several cellular proteins. This is mediated via a calcium-dependent pathway, also activated by a phenethyl ester analogue of CCK and calcium ionophores, and by a protein kinase C-dependent cascade, also activated by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate. All demonstrable stimulated tyrosine phosphorylation events were inhibited by genistein, with different subsets of proteins affected by staurosporine and H-7. The importance of tyrosine phosphorylation events in agonist-stimulated amylase secretion was studied using genistein and staurosporine as protein kinase inhibitors. Genistein inhibited the secretory response to CCK, its phenethyl ester analogue, and calcium ionophores, all known to stimulate secretion in a calcium-dependent fashion. In contrast, genistein had no effect on the secretory response to 12-O-tetradecanoylphorbol-13-acetate, suggesting that the protein kinase C-dependent tyrosine phosphorylation events were not involved in the secretory mechanism. Furthermore, CCK-induced secretion was not affected by relatively specific protein kinase C inhibition by H-7, but was decreased by staurosporine, an inhibitor of both protein kinase C and tyrosine kinase activities in these cells. These results provide evidence that acinar cell tyrosine phosphorylation is stimulated by agonists acting via calcium-dependent and protein kinase C-dependent pathways, with only the calcium-dependent tyrosine phosphorylation cascade involved in triggering hormone-induced amylase release.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Immunoreactive-somatostatin, substance P, and calcitonin gene-related peptide concentrations of the human gastric mucosa in patients with nonulcer dyspepsia and peptic ulcer disease.

Changes in immunoreactive (ir)-somatostatin, substance P, and calcitonin gene-related peptide concentrations of the human gastric mucosa were examined in subjects with nonulcer dyspepsia (NUD) and peptic ulcer to clarify the relationship between these peptides and dyspeptic symptoms. Fifty-six patients with NUD were divided into two subject subgroups as follows: 22 patients with upper abdominal discomfort, nausea, and/or vomiting (motility disorder group) and 34 patients complaining of upper abdominal pain [ulcer-like disorder (UD) group]. These patients were compared with either an age- and sex-matched group of asymptomatic outpatients without any organic disease (control group: n = 51), or to a group with peptic ulcer (PU group: n = 30). Ir-somatostatin concentrations of the gastric mucosa were significantly higher in UD group than in PU, motility disorder, or control group, and ir-substance P concentrations in the UD group were higher than in the PU group. No difference in ir-calcitonin gene-related peptide concentrations was observed among the four groups. These results indicate that there may be two distinct subgroups in NUD, and that NUD is not just a stage within the spectrum of peptic ulcer disease from the viewpoint of several gastrointestinal-hormone concentrations of the human gastric mucosa.

Biopsy↗
PubMed1976

[Motilin-range and analysis of its action].

Motilin is a polypeptide containing 22 amino-acids from the entero-chromaffin cells of the mucosa of the small intestine. Synthetic analogues (13-norleucine-motilin; 13-leucine-motilin) proved to be equal to the natural polypeptide in the biological aspects. Motilin primarily stimulates the motility of the upper gastrointestinal tract but inhibits gastrin evacuation. The contractile action of motilin does not take place by way of the nerves but through receptors on or in the smooth muscle cell itself. Motilin and cyclic adenosine-3':5'-monophosphate are functional antagonists in the contraction of the gastrointestinal musculature. Depending on the dosis, motilin increases gastric pepsin secretion and inhibits protein biosynthesis in the gastric mucosa itself. Radioimmunological motilin tests will help to determine which of the above-mentioned motilin actions are "physiological" and which of them merely "pharmacological".

Animals↗
PubMed1994

EGF stimulates both cyclooxygenase activity and cell proliferation of cultured guinea pig gastric mucous cells.

Epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and insulin all dose-dependently stimulated [3H]-thymidine incorporation into guinea pig gastric mucous cells cultured in vitro. On the other hand, other growth factors, e.g., platelet-derived growth factor (PDGF) and gastrointestinal hormones, such as gastrin, had no effect on DNA synthesis in these cells. Exposure of the cells to EGF at concentrations which stimulated DNA synthesis caused increases in both prostaglandin (PG) E2 release and cyclooxygenase (COX) enzyme protein synthesis, as evaluated by Western blot analysis. These results suggest that such increases in DNA synthesis and PGE2 release may be involved, at least in part, in the mechanism of EGF-induced local regulation of gastric mucosal integrity.

Animals↗
PubMed1994

Nitric oxide and the interrelation between intestinal motility and pancreatic secretion in fasted and fed dogs.

Intestinal motility and pancreatic secretion show synchronous cyclic changes (MMC) that are interrupted by feeding. The aim of this study was to determine the possible implication of nitric oxide (NO) (that was proposed as nonadrenergic noncholinergic neurotransmitter) in the motor and secretory components of MMC in 5 conscious dogs equipped with monopolar electrodes implanted along the small bowel and pancreatic fistulas. In fasted dogs with typical MMCs, L-NNA (an inhibitor of NO synthase) (5 mg/kg-h i.v.) decreased the MMC interval from control value of 80 +/- 7 to 60 +/- 4 min while increasing significantly the slow waves with spikes and suppressing the phase III-related increase in pancreatic secretion. Infusion of L-arginine (L-Arg) (a substrate of NO synthase) (10 mg/kg-h i.v.) increased the MMC interval from control 79 +/- 7 to 96 +/- 8 min and reduced the slow waves spikes by about 25%. Pancreatic secretion showed significant increase to about 20%. CCK maximum. Similar but transient effects were observed when glyceryl trinitrate (GTN) (a donor of NO) (1 mg/kg-h) was administered. After ingestion of meal, the MMC cycles were replaced by irregular spike activity with an average of about 35% slow waves with spikes and pancreatic secretion rose to about 70% of CCK maximum. Infusion of L-Arg (10 mg/kg-h) reduced by about 90% the postprandial spike activity but failed to affect significantly the pancreatic secretion. Also, injection of GTN (1 mg/kg-h) reduced the spike activity but did not influence pancreatic secretion. L-NNA in fed dogs caused an initial increase in spike activity followed by phase III and about 60% inhibition of pancreatic secretion. L-NNA added to L-Arg infusion reversed in part both intestinal motility and pancreatic secretory effects of L-Arg infusion. We conclude that NO system exerts a tonic inhibitory influence on intestinal myoelectric activity by reducing the frequency of MMC pacesetter and by suppressing the postprandial activity but stimulates pancreatic secretion.

Animals↗
PubMedDate not supplied

Gastric ulcer in the elderly.

Our experience shows that neither basal nor pentagastrin-stimulated acid, pepsin, pepsinogen group A and gastrin secretion significantly change across the age spectrum in subjects with peptic ulcer, even though the typical secretory patterns of patients with GU remain well-defined compared to those with duodenal ulcer (DU), even in the later decades of life. Very little is currently known about age-related changes in the various components of the gastric mucosal barrier; however, a significant reduction of the prostaglandin levels in the gastric mucosa of elderly subjects was recently reported. In elderly GU patients, the concentration of neutral glycoproteins and N-acetylneuraminic acid (NANA) was significantly higher than in young adult GU patients perhaps resulting from the migration of the border between the mucosa of the corpus and the antrum that occurs in the aged stomach. Other factors of pathogenetic importance in GU, such as Helicobacter pylori infection, gastroduodenal motility, gastrointestinal hormones, immune disorders and psychological and social characteristics of the elderly should certainly be further investigated. To date, the published data on the treatment of acute GU in the elderly patients concern studies with H2 blockers: famotidine, ranitidine and nizatidine with healing rates ranging from 67.6% to 90.9% after 6 weeks and 83.8% to 96.0% after 12 weeks of treatment. t present the data available on long-term maintenance treatment of GU disease in the elderly are few: a recent randomized, double-blind study conducted on 61 elderly GU patients with nizatidine vs ranitidine both at the dosage of 150 mg/day showed a relapse rate of 8.29% after 6 months and 34.4% after 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Therapeutic uses of gastrointestinal peptides.

The GI tract is one of nature's great pharmacies. Most, if not all, biologically active peptides can be found there, and it is quite likely that others remain to be discovered. Our ability to exploit this resource has expanded considerably over the past two decades. Advances in analytical techniques have allowed investigators to rapidly isolate and purify new compounds from tissue extracts. Sequencing and de novo synthesis of newly discovered peptides are now routine, and the structural modifications required to alter activity and tailor a compound to a particular use are easily made. A number of gastrointestinal peptides or their analogues for use in clinical studies are available from commercial sources (see Table 7). Somatostatin is the first gut peptide to successfully complete development and yield a pharmaceutical compound with a broad range of action. Several of the peptides discussed in this article have similar potential. TRH stands out as a candidate because of its effectiveness in the treatment of experimental spinal cord injury and a variety of shock states. Such a broad range of action in critical fields may justify the intensive development required to yield potent, long-acting, and highly specific analogues. Similarly, the antimetastatic and immunostimulant properties of the enkephalins offer promise for new therapies in the treatment of AIDS, ARC, and cancer. Studies with amylin may lead to new and more precise regimens of blood sugar control in insulin-dependent diabetics and could in turn, prevent some of the worst long-term effects of the disease. The development of effective intranasal forms of GHRH could spare children with GH-GHRH deficiency the distress of repeated injections and help to prevent excessive GH blood levels. Secretin, glucagon, or CGRP might be used one day in cardiovascular emergencies, and VIP or its analogues could prove effective in the treatment of asthma. Although preliminary results with many of these peptides are encouraging, further progress will require the development of standardized experimental models and a more rigorous approach to experimental design. Many of the studies reported here suffered from small patient numbers, a narrow or nonexistent range of doses, or the use of only one or two dosing regimens. Lack of objective criteria for determining the level of response, e.g., in studies of mental illness or degenerative diseases, and the ethical problems of withholding treatment from some patients to establish proper controls further hamper research in this area. If the questions of efficacy and safety are to be resolved, thorough, well-planned trials will be required.

Amino Acid Sequence↗