Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several gastrointestinal peptides with proven or suggested endocrine or paracrine functions influence gastric acid secretion, gastrointestinal motility, and mucosal blood flow. Increased or decreased release of such factors could participate in the pathogenesis of duodenal ulcer disease by inducing increased gastric acid concentration in the duodenal bulb. To date, increased stimulation of parietal cells by gastrin has been demonstrated only in patients with gastrinoma, G-cell hyperplasia, gastric outlet obstruction, hyperparathyroidism, excluded antrum, and short bowel syndrome, but not in the usual duodenal ulcer disease. Also, a defective inhibition of parietal cell function by endocrine or paracrine factors, such as gastric inhibitory polypeptide, secretin, somatostatin and vasoactive intestinal polypeptide, seems not to exist in patients with duodenal ulcer disease. However, as long as the physiology of gastrointestinal peptides in gastric secretion and motility is not understood, a possible role of these factors in the pathogenesis of simple duodenal ulcer disease cannot be excluded.
 ...
PMID:Endocrinology of duodenal ulcer. 51 78

A reliable, sensitive, reproducible and specific radioimmunoassay for cholecystokinin-pancreozymin (CCK) has been developed, using rabbit antisera to highly purified porcine hormone. The natural occurring variant of CCK (39-CCK), in which the ordinary CCK is lengthened from its N-terminus by a hexapeptide, labelled with 125J, and repurified by column chromatography on Sephadex G-10 and on SP-Sephadex C-25, was used as tracer. Separation from antibody-bound labelled 39-CCK was carried out using a double antibody procedure. Non-specific interference with the assay system was abolished by ethanol extractions. Highly purified porcine CCK was used as standard. No significant crossreaction was found with gastrin, motilin, vasoactive polypeptide (VIP), gastric inhibitory polypeptide (GIP), natural and synthetic secretin, pancreatic glucagon or insulin. The sensitivity of the assay is approximately 40 pg/ml of test solution. The mean immunoreactive CCK concentration in 45 fasting normal subjects was 222 pg/ml increasing after food ingestion to 480 pg/ml. Somatostatin was able to abolish the stimulated CCK release. Elevated CCK concentrations were found in chronic pancreatitis. Immunohistochemical identification of pancreozymin cells was carried out either in surgical samples or in biopsy material. Approximately 1650 CCK cells per cross-section in the duodenum of humans have been found. The CCK cells usually appeared elongated, oval or pyramidal in shape and were observed to reach the lumen with their apical cell pole.
 ...
PMID:Estimation of cholecystokinin-pancreozymin (CCK) in human plasma and tissue by a specific radioimmunoassay and the immunohistochemical identification of pancreozymin-producing cells in the duodenum of humans. 56 41

The effects of various polypeptide enterohormones and the tachykinin secretogogue, physalaemin, on electrolyte transport by the main excretory duct of the mandibular gland of the rabbit were studied in vitro. Vasoactive intestinal peptide (VIP, 2 X 10(-11) mol 1(-1)) and gastric inhibitory polypeptide (GIP, 10(-11) mol 1(-1)) reduced nett Na+ movement from lumen to interstitium and VIP also reduced the transepithelial potential difference; the effective concentrations of the two hormones lay within the range of normal plasma concentrations. Gastrin (5 x 10(-7) mol 1(-1)) and synthetic secretin (2 x 10(-7) mol 1(-1)) had similar effects but only at concentrations well above the normal plasma levels. Caerulein, an analogue of the octapeptide of cholecystokinin, had no effect on duct function even at a concentration of 10(-6) mol 1(-1). The potent salivary secretogogue, physalaemin (4 x 10(-8) mol 1(-1)), which is an analogue of Substance P, a putative mammalian enterohormone and neurotransmitter substance, caused a marked increase in ductal Na transport (in rat as well as rabbit). It is concluded that VIP and GIP would normally play a role in determining salivary electrolyte composition and it is postulated that their action may be antagonized by a tachykinin such as Substance P.
 ...
PMID:Modification of salivary duct electrolyte transport in rat and rabbit by physalaemin, VIP, GIP and other enterohormones. 56 44

To determine whether gastrin and cholecystokinin (CCK), recently found in the central nervous sytem, were present in cerebrospinal fluid (CSF), we studied human specimens by sensitive and specific radioimmunoassays for the two related polypeptide hormones. The concentration of gastrin in cerebrospinal fluid from 10 neurologically normal persons ranged from 1.5 to 8.0 pM (mean 3.4 pM), whereas the concentration of CCK ranged from 4 to 55 pM (mean 14 pM). The molecular heterogeneity of gastrin and CCK in CSF was determined by gel chromatography of concentrated fluid monitored by 3 gastrin radioimmunoassays specific for different sequences of gastrin17 and 3 CCK radioimmunoassays specific for different sequences of CCK33. Chromatography revealed that gastrin was present in molecular forms corresponding to gastrin34 ('big gastrin') and gastrin17. CCK was present in molecular forms corresponding to the COOH-terminal octapeptide amide of CCK33 and a fragment corresponding to sequence 25-29 of CCK33. Also, a peptide corresponding to COOH-terminal tetrapeptide amide common to both gastrin and CCK was found. The results indicate that true gastrin as well as CCK are present in CSF, and that both hormones display a molecular heterogeneity similar to that found in extracts of brain tissue.
 ...
PMID:Gastrin and cholecystokinin in human cerebrospinal fluid. Immunochemical determination of concentrations and molecular heterogeneity. 68 12

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".
 ...
PMID:[Motilin-range and analysis of its action]. 78 38

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.
 ...
PMID:[New views on gastrointestinal hormones]. 85 99

1 Intracellular recordings of membrane potentials and input resistance have been made from the exocrine acinar cells of mouse and rat pancreas placed in a tissue bath perfused with Krebs-Henseleit solution.2 The resting acinar cell membrane potential was about -38 mV. The acinar cells were stimulated by cholecystokinin-pancreozymin (CCK-PZ), gastrin and the gastrin-related polypeptides, caerulein and desulphated caerulein. The immediate effect of stimulation with these secretagogues was always a depolarization and a concomitant reduction in input resistance and time constant. Depolarization of the acinar cell membrane by these secretagogues was not abolished in the presence of atropine (1.4 muM).3 These peptide secretagogues were divided into the gastrin group and the CCK-PZ group according to the time course of the depolarizations and the shape of the dose-response curve. The depolarization evoked by the gastrin group returned quickly to the resting level but that evoked by the CCK-PZ group was long lasting. The time course and the dose-response curve for desulphated caerulein was identical with that of gastrin.4 It was confirmed electrophysiologically that the activity of gastrin is exerted by the C-terminal tetrapeptide; but the activity of caerulein depends on the C-terminal heptapeptide, especially the presence in the molecule of the sulphated tyrosyl residue at position 7 (numbering from the C-terminus). The equivalent sulphated tyrosyl residue in CCK-PZ is probably necessary for optimal activity of this polypeptide.5 The dose-response curves obtained by electrophysiological methods indicated that the relative potencies of the peptides on mouse pancreatic acinar cells were caerulein > CCK-PZ > gastrin. Synthetic human gastrin I was found to have a higher potency than either tetra- or pentagastrin.
 ...
PMID:The effects of gastrin and gastrin analogues on pancreatic acinar cell membrane potential and resistance. 88 86

Gastrointestinal myoelectric activity was studied in three conscious fasted dogs with electrodes surgically implanted in the stomach and small intestine, during separate and combined intravenous infusions of 13-norleucine motilin (13-nle-motilin) and pentagastrin (PG). Basal recordings confirmed the presence of regular interdigestive myoelectric complexes (MC's). 13-nle-motilin infusion below 50 ng/kg-h was without effect: higher doses up to 400 ng/kg-h resulted in the interpolation of one or more MC's in the spontaneous sequence. The rate of aboral transit of 13-nle-molitin-induced MC's did not differ significantly from that of spontaneous MC's. When MC's were abolished by feeding or PG infusion, simultaneous 13-nle-motilin administration was without effect on spike activity, but slightly attenuated the accelerating effect of gastrin on the gastric pacemaker frequency. The myoelectric events triggered by 13-nle-motilin suggest that in the conscious dog the polypeptide may not act directly on the smooth muscle cell, as it does in vitro, but through an extra-enteric neural control mechanism which is uncoupled by gastrin.
 ...
PMID:The gastrointestinal myoelectric response to 13-Nle-motilin infusion during interdigestive and digestive states in the conscious dog. 90 76

1. The argyrophil (enterochromaffin-like) cells in the oxyntic gland area of the rat stomach contain histamine, which can be demonstrated fluorescence microscopically after exposure to gaseous OPT. After administration of L-dopa (or L-5-hydroxytryptophan), these cells produce and temporarily store dopamine (or 5-hydroxytryptamine), demonstrable by its characteristic formaldehyde-induced fluorescence. Ultrastructurally, the enterochromaffin-like cells, which have the appearance of polypeptide hormone-secreting cells, comprise two main cell types, the most predominant one having vesicular type granules (EGL cells), the second most predominant one having smaller, uniformly electron dense granules (A-like cells). 2. Rats were subjected to the following surgical treatments: antrectomy; porta-caval shunting; antrectomy+porta-caval shunting; or sham-operation. Three to eight weeks after surgery the histamine-storing cells (enterochromaffin-like cells) of the oxyntic mucosa were analysed by fluorescence histochemistry, light and (quantitative) electron microscopy, and fluorometric determination of amines. 3. After antrectomy, fluorescence histochemistry and silver staining revealed a reduced number of enterochromaffin-like cells. The histamine content in the oxyntic mucosa was reduced by about 50%. As in unoperated injection of pentagastrin seemed to mobilize histamine. Feeding or injection of insulin failed to do so in antrectomized as opposed to control rats. Ultrastructurally, the cytoplasmic granules of both endocrine-like cell types were less numerous than in the unoperated rats. The reduction in cell number and granularity was particularly conspicuous with regard to the EGL cells. 4. After porta-caval shunting the number of enterochromaffin-like cells increased markedly. Chemical determination revealed a twofold increase in the histamine concentration of the oxyntic mucosa. Feeding or injection of insulin or pentagastrin lowered the histamine concentration. As judged by electron microscopy, the proliferation of endocrine-like cells induced by porta-caval shunting was restricted to the ECL cell type. Besides occurring in greater number, these cells were larger than those in unoperated controls, and their cytoplasm was densely packed with granules that were increased in size. 5. Following antrectomy of the porta-caval shunted rats the number of enterochromaffin-like cells and the oxyntic histamine concentration was reduced. 6. The results support the idea that gastrin exerts trophic as well as excitatory effects on oxyntic endocrine-like cells.
 ...
PMID:Effects of antrectomy or porta-caval shunting on the histamine-storing endocrine-like cells in oxyntic mucosa of rat stomach. A fluorescence histochemical, electron microscopic and chemical study. 95 64

Gastrointestinal hormones are considered to be those that are formed in the gastrointestinal tract and there, in physiological concentrations, develop their effects on motility, secretion, trophism, bloodflow and absorption. Structural analysis, synthesis or a high degree of purity after extraction, and its exact demonstration by means of a useful radioimmunoassay, form the basis for the establishment of a polypeptide as a gastrointestinal hormone. To this category belong, at the present time, gastrin, cholecystokinin-pancreozymin (CCK-PZ) and secretin. GIP, VIP, motilin, glucagon and somatostatin are considered likely candidates. The substances gastrin and CCK-PZ, which are structurally related and have a predominantly stimulating effect, and the structurally dissimilar motilin, contrast with the partially or totally inhibiting hormones of the glucagon family, namely, secretin, VIP, glucagon-enteroglucagon, GIP and somatostatin. By the combined action of these hormones with one another and with the autonomic nervous system, the digestive processes are regulated. Disturbances in the formation of these hormones, in particular an overproduction, give rise to disease syndromes that can now be diagnosed and, in part, treated by surgery. The therapeutic application of gastrointestinal hormones has now also become a possibility.
 ...
PMID:[Gastrointestinal hormones]. 96 Sep 54


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>