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

The effect of H2-receptor blockade on intragastric acidity was studied in nine normal males. The pH of their gastric contents was measured at hourly daytime and two hourly nighttime intervals for 48 hours. The subjects ate identical meals, drank identical volumes of fluid, and smoked the same number of cigarettes during the two study days. Their physical activity was unrestricted in a ward environment. Blood cimetidine and plasma gastrin were measured in serial blood samples. The nine subjects were treated in random sequence with cimetidine 0-8-1-0 g on one day and placebo capsules on the other. The drug was given in four divided doses: four subjects received it before, and five after, the three main meals. All took the fourth dose at bedtime. Replicate studies in an additional subject given placebo on both study days showed good reproducibility (r=0-80, P less than 0-01). Cimetidine therapy decreased intragastric acidity in all nine subjects. The decrease was similar in the two groups taking the drug before or after meals, mean 24 h intragastric hydrogen ion activity being lowered by 70 and 72% respectively. Nocturnal anacidity was recorded in only two of 45 samples. Administration of cimetidine before meals produced earlier and higher drug blood levels than post-prandial medication, but when it was taken after food the blood levels were highest at the time when the buffer capacity of the food was waning. Blood concentrations of cimetidine exceeded the secretory IC50 level for most of the time between doses. The results show that cimetidine 0-8-1-0 g/day in four divided doses produces a striking and consistent decrease of intragastric acidity. Although variation in the timing of the dose in relation to meals did not affect the decrease of acidity, the absorption data suggest that patients should take the drug after meals.
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PMID:Effect of cimetidine on 24-hour intragastric acidity in normal subjects. 0 61

By arranging a series of psychological contingencies (unpredictability, uncontrollability, conflict), coupled with delivery of a physical stimulus (electric shock), we produced gastroduodenal mucosal lesions in 7 of 8 rhesus monkeys. The most severe conflict paradigm most consistently produced lesions across subjects. Of the 30 lesions observed by endoscopy, 80% occurred near the anatomic junction of gastric body and antrum, in the antrum, or in the duodenum. Lesions varied in severity from discolorations of the mucosa to disruptions of mucosal integrity. Lesions in the stomach generally disappeared in several days despite the continuation of stress; some duodenal lesions were equally evanescent, but in 2 monkeys, lesions lasted over a week. Hydrogen ion kinetics were measured in 2 monkeys that developed gastric lesions and 2 that developed duodenal lesions. The rate at which hydrogen ion entered the duodenum was uniformly suppressed for all 4 monkeys during their first session of shock avoidance; during their last session, the gastric subgroup continued to show suppression while the duodenal subgroup returned towards control levels. Serum gastrin levels were unchanged by the multiple-stress procedures. Our finding of consistently producible, stress-induced gastroduodenal pathology in anatomic areas similar to those involved in man suggests that the subhuman primate is suitable for further efforts to produce an animal model of psychosomatic ulcer disease.
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PMID:Effect of multiple-stress procedures on monkey gastroduodenal mucosa, serum gastrin, and hydrogen ion kinetics. 2 64

1 An isolated stomach preparation from immature rats is described. The lumen of the stomach was perfused and the hydrogen ion activity of the perfusate recorded continuously. 2 The preparation gave dose-dependent responses to gastrin, acetylcholine and dibutyryl cyclic adenosine 3',5'-monophosphate and these responses were readily reversed on washing out the agonist. 3 The acid secretory response to gastrin was inhibited by metiamide at concentrations of 10(-5) M and 3 X 10(-5)M. 4 The acid secretory responses to acetylcholine and dibutyryl cyclic adenosine 3',5'-monophosphate were not inhibited by concentrations of metiamide up to 10(-3) M. 5 These findings are discussed in relation to the role of histamine in the control of gastric acid secretion.
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PMID:The effect of metiamide on acid secretion stimulated by gastrin, acetylcholine and dibutyryl cyclic adenosine 3',5'-monophosphate in the isolated whole stomach of the rat. 18 71

This study evaluates the structure-function relationships of the C-terminal peptide fragments of gastrin and cholecystokinin (CCK) in the biliary system and the stomach. Dogs with chronic biliary and gastric fistulas were used. Administration of the common fragments of CCK and gastrin with four and five amino acids and the active fragments of CCK with six through eight amino acids without sulfation of tyrosine in position 7 failed to alter hepatic bile flow from control values while significantly stimulating gastric hydrogen ion output. Administration of the seven and eight amino acid peptide fragments of CCK with sulfation of tyrosine in position 7 significantly increased hepatic bile flow. Administration of the sulfated octapeptide with 4 microgram/kg per h of nonsulfated octapeptide did not result in the inhibition of the choleresis produced by the sulfated peptide. The gastric hydrogen ion response produced by the administration of the nonsulfated and sulfated peptide was equal to that of the nonsulfated peptide alone. These results suggest that in the biliary system the receptor is highly specific as sulfation of the peptide fragment of CCK is essential for combining with the receptor, whereas in the stomach the receptor has little specificity and combines with all of the peptide fragments evaluated.
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PMID:Structure-function relationships of peptide fragments of gastrin and cholecystokinin. 19 74

An oral optimum therapeutic dose of poldine was established in 5 normal subjects. Acid secretion in response to a protein meal was measured for 3 hr by continuous intragastric titration with sodium bicarbonate. Poldine 30 min before the meal reduced food-stimulated acid secretion from zero to 60% in the 5 subjects (average inhibition 32%). Poldine inhibited histamine-stimulated acid secretion to approximately the same extent. In separate experiments, gastric acidity after the meal was allowed to seek its natural level (i.e., there was notitration with bicarbonate). Poldine reduced average hydrogen concentration of the gastric contents by 85 to 50% from 1.5 to 3 hr after the meal. Since poldine did not alter the volume or the buffer content of the stomach, poldine inhibition of gastric acidity is due entirely to reduction of acid secretion and not to delayed emptying of food buffer. Poldine had no consistent effect on serum gastrin concentration after the meal when pH was maintained at a constant level by titration with bicarbonate; therefore, poldine inhibition of acid secretion is not mediated by a reduction of serum gastrin concentration.
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PMID:Effect of optimum therapeutic dose of poldine on acid secretion, gastric acidity, gastric emptying, and serum gastrin concentration after a protein meal. 23 1

Cimetidine markedly inhibits gastric acid secretion, but from the therapeutic point of view it is important to know whether concurrent treatment with an anticholinergic increases its effect. This possibility has been investigated by measuring the 24 h intragastric acidity and nocturnal output of acid in four duodenal ulcer patients, each receiving on separate occasions cimetidine 1 g/day and placebo, atropine 2-4 mg/day and placebo, cimetidine and atropine, or two placebos. Cimetidine alone decreased mean hourly hydrogen ion activity by 63% of control values, decreased mean hourly hydrogen ion concentration (total acid) by 41%, inhibited nocturnal acid secretion by 83% and resulted in half the nocturnal samples being anacidic. Atropine alone had no effect when compared with control and combined treatment with both drugs was not superior to cimetidine alone. Atropine did not affect the absorption or urinary excretion of cimetidine. Fasting serum gastrin concentrations were not changed by any of the treatments. At the doses studied, the combination of cimetidine with an anticholinergic appears to offer no advantages over treatment with the H2-antagonist alone. Cimetidine is the only potent anti-secretory drug that does not cause acute side-effects and this important advantage would be lost if it were given with a maximal dose of an anticholinergic.
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PMID:24-hour intragastric acidity and nocturnal acid secretion in patients with duodenal ulcer during oral administration of cimetidine and atropine. 32 18

Seventeen of 37 healthy volunteers participating in studies of acid secretion and 1 patient with Zollinger-Ellison syndrome became rapidly and profoundly hypochlorhydric. A mild illness with epigastric pain occurred in 9 subjects, usually several days before detection of hypochlorhydria. Gastric mucosal biopsy specimens taken from subjects during hypochlorhydria revealed severe fundal and antral gastritis; however, even when acid secretion was severely depressed, parietal cells were abundant and appeared normal histologically. During hypochlorhydria, gastric permeability to hydrogen, sodium, and lithium was normal in 4 subjects. Serum gastrin concentrations were usually normal, whereas serum pepsinogen concentrations were invariably elevated. Serum parietal cell antibodies were not present. Acid secretion returned to near baseline levels in 14 of 17 subjects after a mean of 126 days (range 53--235); severity of gastritis diminished concurrently in 7 of 10 subjects on whom biopsies were serially performed. An infectious etiology is suspected, although serologic studies and bacterial and conventional viral cultures of stool and gastric juice have not identified a candidate agent.
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PMID:Epidemic gastritis with hypochlorhydria. 43 44

The effect of electrical vagal stimulation on canine pancreatic exocrine function was studied in conscious dogs by stimulating intact thoracic vagus nerves, the distal ends of cut vagus nerves in animals with intact gastric denervation, and the distal ends of cut vagus nerves in dogs whose stomachs had been previously selectively denervated. The effectiveness of the stimulus was confirmed by monitoring gastric hydrogen ion output. The results indicate that stimulation of intact nerves produced minimal alteration in pancreatic output and bicarbonate and protein secretion while significantly increasing gastric fistula hydrogen ion output. Stimulation of the distal ends (efferent fibers) of cut vagus nerves in dogs with intact gastric innervation significantly increased the volume and protein output of the pancreas and the acid output of the stomach. Stimulation of the distal ends of cut right and both vagus nerves in dogs whose stomach had been denervated previously, again, significantly increased the volume and protein output of the pancreas without stimulation of stomach hydrogen ion output. The data presented in this study suggest that the canine pancreas is innervated directly by vagal fibers, which when stimulated produce an increase in protein (enzyme) output and volume of secretion. Maintenance of the pancreatic response following denervation of the stomach suggests that the response is primarily the result of direct vagal innervation and is not produced by gastrin released from the antrum.
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PMID:The effect of electrical vagal stimulation on canine pancreatic exocrine function. 114 32

Although Helicobacter pylori is now accepted as the major aetiological factor in chronic gastritis in man, many of the factors which determine its pathogenicity are unknown. The organism has adapted to survive in the low-pH environment of the stomach, partly through its ability to buffer hydrogen ion by the hydrolysis of urea and by the presence of lectins on its surface, which bind to gastric mucosa and epithelial cells. After attachment, harmful toxins and enzymes have access to the gastric cells and cellular damage and an immune response ensues. In patients with duodenal ulceration, Helicobacter pylori-related gastritis predominantly affects the gastric antrum and has a high prevalence. Excessive gastrin production has been suggested as a potential aetiological factor linking infection with duodenal ulcer development. Perhaps more important is the association between gastric metaplasia of the duodenal epithelium, which is correlated with acid load and is more extreme in H. pylori positive patients with duodenitis. Organisms may subsequently spread from the gastric antrum into areas of gastric metaplasia in the duodenal bulb, leading to areas of chronic duodenitis and ultimately frank ulceration. It should not be overlooked, however, that other factors such as genetic predisposition, blood group, stress, drugs and smoking all have a role to play in the outcome, given the comparatively small number of patients in the general population infected with H. pylori who develop ulcer disease.
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PMID:Role of Helicobacter pylori in gastritis and duodenitis in man. 144 34

Gastrocystoplasty is used to augment the bladder of patients with decreased renal function to prevent development or worsening of metabolic acidosis. We recently observed a perforated peptic ulcer in the gastric portion of a defunctionalized gastrocystoplasty. We postulated that the lack of buffering action of urine precipitated peptic ulcer disease in the gastrocystoplasty. To explore this possibility further, we conducted an experiment. In 12 adult female mongrel dogs (weight 15 to 26 kg.) the bladder was divided into right and left segments. One kidney was removed and both hemibladders were capped with a vascularized segment of gastric body. Thus, 1 side (wet) remained exposed to urine, while the other side (dry) was drained to the abdominal wall with a cystostomy tube. The animals were divided into 2 groups: 9 in group 1 received no drugs to modify gastric secretion and 3 in group 2 received a hydrogen (H2) blocker. Three animals in group 1 had perforation of the vesical part of the dry gastrocystoplasty 2 to 3 weeks postoperatively and were sacrificed. The others were sacrificed 3 to 6 weeks postoperatively. Serum gastrin levels remained normal in all animals. Gross and histological examinations of the augmented bladders in group 1 revealed ulcerations of the bladder segment of the wet and dry gastrocystoplasties but the lesions were more numerous and prominent on the dry side in all animals, particularly those in which the perforations occurred. A peptic ulcer was noted in the gastric portion of the dry gastrocystoplasty in 1 animal. The bladder epithelium of the dry gastrocystoplasty showed glandular metaplasia in several animals in this group. In group 2 the wet gastrocystoplasty showed normal histology except in 1 dog that had mild inflammation and focal superficial ulceration in the vesical portion. On the other hand, the dry gastrocystoplasty showed severe inflammation and ulcerations in 2 animals, and mild inflammation of the vesical portion in 1. There were no perforations in this group. This experiment demonstrates that gastrocystoplasty produces cystitis but that these changes are more prominent in the absence of urine, as indicated by the severity of the lesions, perforations and metaplasia. Peptic ulcer disease occurred in the gastric portion of the dry gastrocystoplasty in 1 animal. The use of H2 blockers decreases the incidence of ulceration in wet gastrocystoplasty but it seems to have less influence on the ulceration of dry gastrocystoplasty. Clinicians must be alerted to the risk of perforation of dry gastrocystoplasty.
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PMID:The influence of urinary diversion on experimental gastrocystoplasty. 164 May 24


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