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PubMed1999

Age-related stimulation by tetragastrin of gastric mucin biosynthesis in rat.

The effects of tetragastrin on gastric mucin biosynthesis in middle-aged rats were compared with those in young rats. The incorporation of [3H]glucosamine and [35S]sulfate into mucin was stimulated by tetragastrin in cultured corpus mucosa from 7-week-old rats. In contrast, tetragastrin could not enhance mucin biosynthesis in stomachs from 52-week-old rats. The isosorbide dinitrate-induced stimulation of corpus mucin biosynthesis observed in middle-aged rats was essentially the same as that seen in young rats. Nitric oxide (NO) synthase activity of the corpus was significantly reduced in the middle-aged rats compared to the young rats. NO synthase-immunoreactivity was observed at surface mucous cells in the corpus mucosa of young, but not of middle-aged, rats. These results suggest that aging decreases the effect of gastrin on gastric mucin biosynthesis through the age-related loss of NO synthase function in the surface mucous cell layer of rat stomach.

Aging↗
PubMed1989

Enhancement by tetragastrin of experimental induction of gastric epithelium in the duodenum.

The effects of tetragastrin and truncal vagotomy on the incidence of gastric type epithelium in the duodenum by intraduodenal instillation of 5% NaOH solution were investigated in Wistar rats. Prolonged administration of 1 mg tetragastrin/kg body weight in depot form starting one week after NaOH treatment resulted in a significant increase in gastric acid secretion and the incidence and number of villi with gastric epithelium in the duodenum in experimental week 10. Villi with gastric epithelium were found in five (23%) of 22 rats in control group, whereas abnormal villi were found in 13 (59%) of 22 rats in the tetragastrin treated group (p less than 0.05). The average number of villi with gastric epithelium rose from 0.6 (0.4) per 100 villi in control rats to 2.4 (0.6) per 100 villi in tetragastrin treated rats (p less than 0.01). On histological examination, gastric type epithelium was most often found on stunted or flattened villi, and was always within the boundaries of the area of Brunner's glands. These mucosal changes reverted toward normal with time. In week 35, the incidence of gastric epithelium was significantly less than at week 10 (p less than 0.05). In contrast, no villi with gastric epithelium were found in vagotomised rats in week 10 (p less than 0.05). Vagotomy also caused a significant decrease in gastric acid secretion. These results show that exposure of the duodenal mucosa to high levels of gastric acid enhance the induction of gastric eithelium in the duodenum.

Animals↗
PubMed1998

Distinct effects of tetragastrin, histamine, and CCh on rat gastric mucin synthesis and contribution of NO.

Although gastrin, histamine, and carbachol (CCh) accelerate gastric mucin metabolism, information about their target cells of mucin production is lacking. To clarify this, we examined the effects of these stimulants, including the possible participation of nitric oxide (NO), on mucin biosynthesis in distinct sites and layers of rat gastric mucosa. Pieces of tissue obtained from the corpus and antrum were incubated in a medium containing radioactive precursors and each stimulant, with or without NO synthase (NOS) inhibitor. Distribution of NOS was compared with that of the specific mucins by immunostaining using specific antiserum and monoclonal antibodies. In the full-thickness corpus mucosa, tetragastrin enhanced [3H]glucosamine incorporation into mucin but had no effect on [14C]threonine incorporation. Both histamine and CCh dose dependently increased 3H- and 14C-labeled corpus mucin. Only CCh stimulated antral mucin biosynthesis. CCh stimulation was noted in the corpus mucosa after removal of surface mucous cells, but stimulation by tetragastrin or histamine disappeared as a result of this pretreatment. Only tetragastrin-induced activation was completely blocked by the NOS inhibitor. NOS immunoreactivity was limited to surface mucous cells. Mucus-producing cells present in the different sites and layers of the gastric mucosa have distinct mechanisms for regulation of mucin biosynthesis. Gastrin-stimulated mucin biosynthesis mediated by NO is limited to surface mucous cells of rat gastric oxyntic mucosa.

Animals↗
PubMed1984

'In vivo' amplification of biological activity of tetragastrin by amino acid hydroxamates.

Rat blood was shown to contain an aminopeptidase which rapidly hydrolyses short peptides containing an aromatic amino acid as N-terminal residue. Using tetragastrin (Trp-Met-Asp-PheNH2) as substrate, we showed that some amino acid hydroxamates inhibit rat aminopeptidase activity 'in vitro' in the following order: HTrpNHOH greater than HPheNHOH much greater than HAlaNHOH. The same hydroxamates markedly enhanced the biological activity of tetragastrin 'in vivo'. The amplification of the secretory effect, correlated with the amount of the hydroxamate used, strongly suggests that these compounds can stabilize a number of active peptides in vivo by inhibiting their proteolytic degradation.

Amino Acids↗
PubMed1988

Increased parietal cell responsiveness to tetragastrin in patients with recurrent duodenal ulcer.

To clarify the contributive factors in the recurrence of duodenal ulcer, the present study was carried out on 65 male patients with active duodenal ulcers and 20 healthy male subjects. After having verified that the ulcer had healed, gastric acid secretory responses to graded doses of tetragastrin from 62.5 to 16,000 ng/kg/hr were investigated using a logarithmic transformation model. Several clinical features were also investigated. The patients were divided into three groups based on the later endoscopic follow-up study for two years. The early-recurrent group included 16 patients with recurrence occurring within three months. The late-recurrent group included 25 with recurrence occurring after three months. The nonrecurrent group included 24 patients without recurrences during the follow-up period. The 20 healthy male subjects were defined as a control group. The results were as follows: (1) Significant differences were not discerned either in basal and peak acid outputs between the three patients groups. (2) The ED50 value for tetragastrin was lower in the early-recurrent group than in the other three groups. (3) The early-recurrent group showed a higher percentage of smokers than the other patient groups. These results suggest that smoking and increased parietal cell responsiveness correlates strongly with duodenal ulcer recurrence.

Adult↗
PubMed1978

Fine morphology of the secretory mode of the tetragastrin-stimulated chief cells of human and dog gastric mucosa.

The chief cells of the gastrin-stimulated gastric mucosa of human and dog were observed under a light and electron microscope. Four microgram/kg AOC-tetragastrin were given parenterally by a single shot to a man and three dogs respectively. Pepsinogen in the gastric mucosa increased at the wash-out stage and at the following dynamic equibrium stage of the chief cell secretion cycle after the administration of AOC-tetragastrin. During those stages, the chief cells released zymogen granules intensively. As the main ultrastructural process for releasing the zymogen granules, the emiocytosis in man and the apical cytoplasm dissociation in dog were discussed.

Adult↗
PubMed1983

Cholinergic stimulation of pancreatic polypeptide release by a meal, bombesin, neurotensin, tetragastrin, cholecystokinin, and cerulein.

It has been demonstrated that pancreatic polypeptide (PP) release can be markedly impaired by vagotomy or anticholinergic drugs. The current studies examine the role of cholinomimetic stimulation on PP release in dogs. Eight conscious animals underwent a series of tests: (1) a test meal (10 g/kg Alpo); (2) tetragastrin infusion (4 micrograms/kg/hr); (3) bombesin infusion (1.0 microgram/kg/hr); (4) cerulein infusion (100 ng/kg/hr); (5) cholecystokinin octapeptide (CCK-OP) infusion (100 ng/kg/hr); (6) neurotensin infusion (3 ng/kg/hr). All the studies were repeated individually with intravenous bethanecol (100 micrograms/kg/hr) as the background stimulant. The mean increment of PP released by a meal (160 +/- 32 fmol/ml) was significantly increased by bethanecol infusion (316 +/- 49 fmol/ml) (P less than 0.05). Each individual peptide released a significant amount of PP; tetragastrin: 53 +/- 11; neurotensin: 58 +/- 14; CCK-OP: 42 +/- 9; cerulein: 42 +/- 12; bombesin: 118 +/- 24 (P less than 0.05). Bethanecol did not significantly augment PP release by any of the individual peptides (P greater than 0.05). This study indicates that PP release by a meal is sensitive to cholinomimetic stimulation and that the peptide involved is neither gastrin, neurotensin, CCK, bombesin, nor cerulein. These data support the possibility of the existence of a cholinergic stimulatable mechanism, possibly a peptide responsible for the release of PP.

Animals↗
PubMed1998

Interleukin-8 enhances tetragastrin-stimulated acid secretion in vivo.

Recent studies have demonstrated a relationship between cytokines and gastric acid secretion. However, details of the mechanism underlying that relationship have not been elucidated. For this study, an in vivo experiment was undertaken to investigate the possibility that IL-8 would be involved in the mechanism of gastric acid secretion. Gastric lumen-perfused rats were prepared and the stomachs were perfused with a saline solution. The effluent was collected at 15-min intervals and assayed for titratable acid against 0.01 M NaOH. IL-8 (200 ng/rat) given intravenously did not influence basal acid output in rats. However, when IL-8 was administered by injection during continuous tetragastrin infusion (4 microg/kg/hr) acid output increased significantly (P < 0.01). The acid output during the first hour following IL-8 injection was 43.6% higher than prior to the injection. Acid output during the second hour was lower than during the first hour. However, successive injection of IL-8 again increased tetragastrin-stimulated acid output by 23.4% (P < 0.05). IL-8 injection did not change histamine-stimulated acid output. The results indicate that IL-8 has the effect of enhancing gastrin-stimulated acid secretion and might have an important role in the pathophysiology of gastric acid secretion in vivo.

Animals↗
PubMed1979

Trophic effect of tetragastrin on the stomach, duodenum and pancreas in rats.

Subcutaneous injections of a large dose of tetragastrin (2 mg/day) into a rat for 4 weeks caused hypertrophy of parietal cells of the stomach, intestinal glandular cells of the duodenum, and pancreatic acinar cells. Ths histometrical analysis revealed that these trophic effects of tetragastrin were produced in varying degrees in different sites.

Animals↗
PubMed1997

An immuno- and enzyme cytochemical study of the H(+)-K+ ATPase in human parietal cells after administration of tetragastrin and omeprazole.

The presence of subunit proteins, 1H9 for the alpha-subunit and 2B6 for the beta-subunit, of H(+)-K+ ATPase and its activity in tubulovesicles and intracellular canaliculi of gastric parietal cells were immunocytochemically and enzyme cytochemically examined. Specimens were taken from healthy human volunteers by endoscopic biopsy in resting, tetragastrin-stimulated and omeprazole-inhibited conditions. H(+)-K+ ATPase was present in both intracellular canaliculi and tubulovesicles in these three conditions. Gold particles of the alpha-subunit decreased in number, and those showing the beta-subunit increased under both gastrin-stimulating and omeprazole-inhibiting conditions compared with parietal cells in the resting state. We suggest that the administration of tetragastrin and omeprazole alter the turnover rate of each subunit of H(+)-K+ ATPase, resulting in the difference of the proportions of alpha- and beta-subunits. Moreover, the activity of H(+)-K+ ATPase was detected strongly beneath the membrane of microvilli and weakly in that of tubulovesicles under these three conditions. After 7 days of daily oral omeprazole intake, H(+)-K+ ATPase in parietal cells were detected in intracellular canaliculi and tubulovesicles. However, the H(+)-K+ ATPase activity in tubulovesicles was diminished 1 h after omeprazole intake, and the activity in intracellular canaliculi was completely inhibited even 3 h after omeprazole administration. These results show that omeprazole inhibited the H(+)-K+ ATPase activity in both intracellular canaliculi and tubulovesicles.

Adult↗
PubMed1978

A scanning electron microscopic study on the fractured rat parietal cells in resting state and after stimulation with tetragastrin.

Parietal cells in the rat gastric mucosa fractured by freeze cracking methods under resting (control) state and tetragastrin stimulation were studied by field emission scanning electron microscopy. The structures thus revealed were compared with those studied by transmission electron microscopy. In the fractured cytoplasm, intracellular canaliculi lined by numerous microvilli invaginated deeply towards the basal cytoplasm. Tubulovesicles appeared as many small holes about 0.05mu in diameter and were distributed predominantly in the apical or pericanalicular cytoplasm. Some tubulovesicles directly opened into the secretory canaliculi. Occasionally, tiny microvilli appeared in tubulovesicles. After being stimulated for 30 min with tetragastrin, the secretory canaliculi of parietal cells became enlarged and there were a concomitant increase in both the number and size of microvilli. Tubulovesicles also were increased in size and number and the tiny microvilli in them were also increased. The tubulovesicles were enlarged presumably as a result of membrane fusion between contiguous tubulovesicles. It was found that the enlargement of the secretory canaliculi was the result of fusion of the membrane of a single tubulovesicle or a confluence of tubulovesicles to that of the secretory canaliculus and the successive disappearance of the fused membrane.

Animals↗
PubMed1978

Comparison of the early time courses of the release of insulin that follow injections of tetragastrin, tolbutamide, xylitol, and glucose into the pancreatic artery of dogs.

The early time courses of insulin release were studied by injecting insulinotropic substances directly into a dog's pancreatic artery. Blood samples from the pancreatic vein were collected every five seconds continuously over 90 seconds and were assayed for their insulin concentrations. Injections were repeated two to five times, with intervals of 30 minutes. Insulin release was stimulated within one minute after injection of each of tetragastrin, tolbutamide, xylitol, and glucose, but the time courses of the release of insulin were different with different stimulants: Tetragastrin and tolbutamide increased insulin release faster than did glucose; xylitol produced a slower insulin release than did glucose. The slower insulin-releasing effects of glucose and xylitol than the other agents would be compatible with the theory that their metabolism is required to cause release of insulin, but it is also possible that the glucoreceptor mechanism may require a longer lag time than the other receptor mechanisms for the perception and transfer of the signal to release insulin.

Animals↗
PubMed1999

Effect of exogenous tetragastrin on gastric myoelectrical activity in humans.

It is known that cutaneous electrogastrography (EGG) undergoes a change after food ingestion, showing increases in frequency and amplitude compared with preprandial values, but the factors regulating such changes remain to be elucidated. Paying special attention to gastrin, one of gastrointestinal peptides released after food ingestion, we administered tetragastrin in an exogenous manner and evaluated its effects on EGG in the present study. In healthy subjects, the intramuscular injection of tetragastrin significantly increased EGG frequency dose-dependently, but caused no significant change in amplitude. These results suggest that the increase in endogenous gastrin release is one of the mechanisms which underlies the increase in EGG frequency after food ingestion.

Adult↗
PubMed1991

[Conformational-functional relationships of tetragastrin analogs].

Sets of low-energy backbone conformations of the active tetragastrin analogue Boc-Trp-Leu-Asp-Phe-NH2 and two competitive antagonists Boc-Trp-Leu psi (CH2NH)-Asp-Phe-NH2 and Boc-Trp-Leu-Asp-O-CH2-CH2-C6H5 were obtained using theoretical conformational analysis methods. Groups of the conformations were selected for the three analogues, allowing a spatial matching of Trp, Asp and Phe residues responsible for the gastrin receptor binding. Three conformations possessing the lowest energies among the geometrically similar structures of these three peptides are suggested as a model for the "receptor-bound" conformations of these analogues. Backbone spatial folding resembling an alpha-helix turn is characteristic of these conformations. The correspondence of the proposed model to the available data on structure--activity relationships for tetragastrin analogues is discussed. Orientations of the putative receptor-bound conformations in a "water--lypophylic medium" two-phase system were investigated.

Amino Acid Sequence↗
PubMed1994

Conformation of tetragastrin in DMSO. Monte Carlo simulation taking account of solvent effects.

A conformation analysis of tetrapeptide in DMSO was carried out by the Monte Carlo simulation including the solvent effects in the energy function. The lowest energy conformations in the zwitterionic and cationic states are a similar compact form, in which the two aromatic rings are close to each other. The distance distributions between the specified atoms in the molecule show that most conformations in the local energy minima are similar to this folded conformation, although there is another type of conformation of interest, which has an extended form with the two separate aromatic rings. Such results are consistent with the NMR and CD experiments, and suggest that the compact form of tetragastrin is essential as a biological active conformation. The folded structure is stabilized by the solute-solvent interaction. In particular, the nonbonding interactions between the solute and solvent molecules cause a folding effect on the molecular conformation in total. This study is a first case taking account of the solvent effect into the conformation analysis of tetragastrin.

Amino Acid Sequence↗
PubMed1976

Plasma human calcitonin (hCT) levels in normal and pathologic conditions, and their responses to short calcium or tetragastrin infusion.

Plasma hCT levels were less than 50 pg/ml in 50 normal subjects. In 16 patients with medullary carcinoma of the thyroid (MCT), plasma hCT levels were distinctively elevated and they fell significantly after total thyroidectomy, but in 11 of them plasma levels were still high, indicating the presence of metastases. In 74 patients with the other types of malignancy, plasma hCT levels were found to be high in 9 cases (3 oat cell carcinoma of the lung, 4 malignant carcinoids, one malignant pheochromocytoma and one acute myelocytic leukemia). Except for the leukemic case, all these tumors were derived from neural crest. In 12 patients with primary hyperparathyroidism, plasma hCT levels were less than 20 pg/ml. In 13 hypoparathyroid patients, two with pseudohypoparathyroidism and one with pseudoidiopathic hypoparathyroidism, plasma hCT levels were slightly elevated. Some patients with uremia had elevated plasma hCT levels, but there was no relation between plasma levels of hCT and those of PTH, urea nitrogen or creatinine. In response to Ca (4.5 mg/kg/10 min) or tetragastrin (4 mug/kg/5 min) infusion, a marked increase in plasma hCT was observed in all patients with MCT, but not in normal subjects. In 5 hypoparathyroid patients, a significant increase to both stimuli was also observed in all cases. Two patients with pseudopseudohypoparathyroidism responded to the Ca load. These results indicate that the determination of plasma hCT levels especially after a short Ca or tetragastrin infusion is important to study various pathological conditions.

Calcitonin↗
PubMedDate not supplied

[The effect of pentagastrin and ornithine-tetragastrin on motor activity of the stomach in skates and scorpion-fish].

Low doses of pentagastrin (50 mug/kg b. w.) have no physiological effect on motor activity of the stomach in the skate Dasyatis pastinaca. Average doses (100-200 mug/kg) stimulate the activity, whereas high ones (300 mug/kg) inhibit the frequency of stomach contractions, slightly increasing their amplitude. Ornithine tetragastrin in a dose 2000 mug/kg does not affect motor activity of the stomach in skates. In the scorpion-fish Scorpaena porcus, ornithine tetragastrin (1000 and 2000 mug/kg) inhibits motor activity of the stomach.

Animals↗
PubMed1993

pH profile of esophagus in patients with inlet patch of heterotopic gastric mucosa after tetragastrin stimulation. An endoscopic approach.

In a series of 1771 endoscopic examinations from 1988 to 1990, we observed 62 cases (3.3%) of inlet patch of heterotopic gastric mucosa (IPHGM) in the upper esophagus. Ten of the IPHGM patients complained of throat discomfort or globus sensation, and these symptoms were relieved by histamine H2-antagonists, suggesting that these symptoms could be caused by acid secretion from IPHGM. Acidity under tetragastrin stimulation was measured in the esophagus and compared with the pool of gastric juice and saliva under direct vision by a newly devised endoscopic method. Congo red staining was also carried out after pH measurement. Significant pH reduction at IPHGM was observed in three cases, and black coloration with Congo red staining in the IPHGM was observed in four cases. These findings suggest that IPHGM is a mucosal change with latent acid secretion.

Adult↗