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)

Although increased gastric acidity may be important in the pathogenesis of duodenal ulcer, it has a less well-defined role in the formation of gastric ulcers. The present study was undertaken to determine (1) the 24-hour intragastric pH and serum gastrin profiles of 31 patients with duodenal ulcers, eight patients with gastric ulcers, and seven healthy volunteers and (2) the effect of 600 mg of cimetidine BID on these measurements. There was considerable overlap of basal acid output values in the three groups, and mean values did not differ significantly. In response to pentagastrin, the peak acid output was significantly higher in the duodenal ulcer group than in the gastric ulcer or healthy group. There were no intergroup differences in intragastric hydrogen ion (H+) activity after meals, overnight, and over 24 hours, when all subjects received placebo. However, the pH values remained at or above 4.0 for a longer period during the night in the gastric ulcer patients than in the duodenal ulcer patients or healthy subjects. There were no intergroup differences in basal gastrin concentration, but the postprandial gastrin response after each meal was higher in the gastric ulcer group than in the other two groups. In the gastric ulcer group, cimetidine suppressed H+ activity at all times; in the duodenal ulcer and healthy groups, cimetidine suppressed H+ activity only after breakfast, overnight, and over 24 hours. Cimetidine enhanced the serum gastrin response to food to a greater extent in the ulcer patients than in the healthy subjects. In the healthy subjects, the ratio of H+ to gastrin (H+:G) was higher than in the duodenal or gastric ulcer patients but was suppressed only minimally by cimetidine, whereas cimetidine markedly suppressed the H+:G ratio in both groups of ulcer patients. Patients with a history of duodenal or gastric ulcers differed from healthy volunteers in their food-stimulated gastrin response and in their H+:G ratio when treated with cimetidine. Intergroup differences in gastrin response to food, but not in intragastric pH in response to food, suggests that defective control of or response to gastrin may be important in the pathogenesis of acid-peptic disease. Cimetidine, which was effective in H+ suppression in all subject groups, may alter the sensitivity of the parietal cells to gastrin in patients with duodenal or gastric ulcers.
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PMID:Interrelationship between gastric acidity and gastrin concentration in patients with duodenal or gastric ulcer and in healthy subjects. 401 26

The role of endogenous prostaglandins in the physiologic regulation of gastric secretion is unclear. We evaluated the effect of indomethacin, an inhibitor of endogenous prostaglandin synthesis, on basal gastric secretion in humans using a two-component model for calculating gastric acid and bicarbonate secretion. After a control, gastric secretory study, 11 healthy volunteers were given 50 mg of indomethacin orally every 8 h for a total of 10 doses, after which the gastric secretory experiment was repeated. Indomethacin significantly (p less than 0.05) increased basal gastric juice volume, hydrogen ion concentration, osmolality, and acid output. Indomethacin increased acid secretion significantly (from 4.9 +/- 1.2 to 7.4 +/- 1.7 mmol/75 min, p less than 0.02) without affecting gastric bicarbonate secretion (control 2.7 +/- 0.8, indomethacin 3.0 +/- 0.7 mmol/75 min; p greater than 0.05). The increase in basal acid secretion after indomethacin administration was quite variable from subject to subject and was unaccompanied by significant changes in basal serum gastrin concentrations. Unlike basal acid secretion, indomethacin had no significant effect on acid secretion stimulated by intragastric infusion of homogenized food. Moreover, indomethacin did not prevent intravenous somatostatin 14 from inhibiting food-stimulated acid secretion, in contrast to a previous study in rats in which indomethacin blocked the inhibitory effect of somatostatin on acid secretion. Assuming the effect of indomethacin is due to reduced endogenous prostaglandin synthesis, we conclude that (a) in some individuals endogenous prostaglandins suppress basal acid secretion by a mechanism independent of the hormone gastrin; (b) endogenous prostaglandins play little, if any, role in the regulation of basal bicarbonate secretion by the stomach; and (c) endogenous prostaglandins do not regulate food-stimulated acid secretion, nor do they mediate the inhibitory effect of somatostatin on gastric acid secretion in humans.
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PMID:Effect of indomethacin on gastric acid and bicarbonate secretion in humans. 614 64

Paired indirect immunoenzyme staining based on primary antisera from the same species was performed sequentially without intermediate antibody elution. The first antigen was labelled brown by an immunoperoxidase procedure (either the two-stage indirect method, the unlabelled antibody peroxidase-antiperoxidase method, or the avidin-biotin bridge method using diaminobenzidine (DAB) and hydrogen peroxide as the substrates. The second antigen was labelled blue by applying a two-stage indirect immuno-alkaline phosphatase procedure using naphthol AS phosphate and Fast Blue BB salt as the substrate. In this way, polyclonal mucosal immunocytes were revealed in distinctly contrasting colours when stained for kappa and lambda light chains. Glucagon and somatostatin (D) cells in human pancreatic islets, and gastrin and D cells in human gastric antral glands, were likewise clearly differentiated. Conversely, a mixed colour appeared in some immunocytes after staining for alpha and kappa chains. However, unbalanced colour mixing was sometimes difficult to interpret, and additional experiments demonstrated that unwanted interactions could take place between the two sequences of reagents if the density of the DAB deposits was insufficient. These pitfalls were incompatible with unequivocal double staining in the same cell. Nevertheless, paired staining could be conveniently applied with the described procedures when prior knowledge had established that the antigens in question were located in separate cells.
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PMID:Paired indirect immunoenzyme staining with primary antibodies from the same species. Application of horseradish peroxidase and alkaline phosphatase as sequential labels. 620 74

The mechanism of action of gastrin was investigated using cytochemical quantitation of hydroxyl ion production (HIP) in guinea pig gastric oxyntic mucosa. The reaction depends upon the trapping of OH ions produced during gastric stimulation and is blocked by the benzimidazole, Hassle 149/94, which inhibits the K+ + H+-ATPase and by acetazolamide, an inhibitor of carbonic anhydrase activity. It is thus a measure of hydroxyl ions produced during stimulation of the oxyntic cell and reflects upon hydrogen ion production. Gastrin (2.5 X 10(-16) -2.5 X 10(-12) M) caused a linear dose-dependent stimulation of HIP in the oxyntic cells. The response was biphasic, with an early peak at 90 s and a secondary rise at 240 s, which persisted for 10 min. Natural human gastrin (sulfated and nonsulfated) and the active COOH-terminal octapeptide fragment of gastrin stimulated HIP, whereas the biologically inert NH2-terminal (1-13) fragment of gastrin had no effect. The activation of oxyntic cell HIP by gastrin was neutralized by an antiserum directed towards the COOH-terminus of gastrin and not by nonimmune serum. Cimetidine (10(-5) M) blocked 25% and atropine (10(-5) M) had no effect on gastrin-stimulated HIP. EGTA (10(-3) M) and LaCl3 (10(-3) M) inhibited the action of gastrin by 67 and 52%, respectively. The calmodulin antagonists, trifluoperazine (10(-5) M), pimozide (10(-5) M), and the naphthalene sulfonamides, W-7 and W-13 (10(-5) M), inhibited gastrin-stimulated HIP by 45.6 38.5, 42.3, and 37.2%, respectively. Higher doses of W-7 and W-13 (10(-4) M) inhibited gastrin-stimulated HIP by 83 and 67%. The Ca2+ ionophore, A23187 (10(-4) M), stimulated HIP. Thus, it appears that gastrin stimulation of HIP is complex. 25% of its action is via a histamine-dependent pathway. 45% of its action is dependent upon extracellular Ca2+. Its action is also in part dependent upon a Ca2+/calmodulin mechanism.
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PMID:Action of gastrin in guinea pig oxyntic cells. Studies using quantitative cytochemistry. 633 Jan 72

The effect of 600 mg of cimetidine given twice daily on 24-hour intragastric hydrogen ion (H+) concentration was compared with that of the standard regimen of 300 mg of cimetidine given four times daily in six patients with asymptomatic duodenal ulcer. According to the double-blind, Latin-square, repeated-measures design, all subjects followed each cimetidine regimen and a placebo regimen for one week. Acid secretion studies and determinations of drug and gastrin levels in the blood were carried out on the last day of each treatment week. Although 600 mg of cimetidine BID suppressed H+ after breakfast and during the night, compared with placebo treatment (P less than 0.01), the 300-mg QID regimen suppressed H+ only after breakfast and supper (P less than 0.05). A higher percentage of pH readings greater than or equal to 3.0 were obtained with 600 mg of cimetidine BID than with 300 mg of cimetidine QID during the night (P less than 0.05); compared with percentages when placebo was taken, the percentages of pH readings greater than or equal to 3.0 were greater both overnight and during a 24-hour period only when 600 mg of cimetidine was given BID (P less than 0.01). The observed difference in intragastric H+ suppression after each regimen could not be explained by variations in serum concentrations of cimetidine or serum concentrations of gastrin. Despite similar peaks of serum cimetidine after evening doses of 300 or 600 mg of cimetidine, nocturnal intragastric acidity was lower in subjects given 600 mg BID. Further, H+ levels after lunch were similar in both cimetidine-treated groups, despite markedly higher serum cimetidine concentrations in patients receiving 600 mg BID. Pharmacokinetic studies showed equivalent elimination half-times and 24-hour areas under the curve of serum cimetidine concentration in patients on the two cimetidine regimens. Postprandial integrated gastrin responses were of similar magnitude in patients on either cimetidine regimen. There was no significant difference in mean serum gastrin concentrations during the night in placebo-treated and cimetidine-treated patients. Only a weak correlation was observed between H+ and serum gastrin concentration. Although a fluctuation of the H+:gastrin ratio occurred after each meal in all groups, the ratio was suppressed by both dosages of cimetidine. The findings suggest that a regimen of 600 mg of cimetidine BID is superior to the standard regimen of 300 mg QID in suppressing intragastric acidity in patients with asymptomatic duodenal ulcer.
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PMID:Comparative effects of two cimetidine regimens on 24-hour intragastric acidity in patients with asymptomatic duodenal ulcer. 637 6

Both pirenzepine and cimetidine have been shown to be beneficial in the healing of duodenal ulcers. The aim of the present study was to determine the effects of 50 mg of pirenzepine BID and 600 mg of cimetidine BID, either alone or in combination, on 24-hour intragastric acidity, nocturnal gastric secretory volume and acid output, and serum gastrin profile in patients with duodenal ulcers. Eight asymptomatic patients with healed duodenal ulcers received placebo, pirenzepine, cimetidine, or cimetidine plus pirenzepine for one week each in a sequential order. All measurements were performed over a 24-hour period on the last day of each treatment week. Compared with pirenzepine, cimetidine was associated with lower hydrogen ion (H+) activities after breakfast, during the night, and over the 24-hour period. Pirenzepine alone failed to suppress H+, but the combination of cimetidine plus pirenzepine resulted in more prolonged acid suppression, with lower H+ after lunch, than did cimetidine alone. The effect of cimetidine on the suppression of nocturnal acid secretory volume and acid output was further enhanced by the addition of pirenzepine. The fasting serum gastrin concentrations were similar in all treatments, excluding one patient with antral G-cell hyperplasia; the postprandial gastrin responses were similarly higher with cimetidine and cimetidine plus pirenzepine than with pirenzepine. The findings suggest an added benefit of combination therapy with cimetidine and pirenzepine that may be useful in patients who fail to respond to single-agent therapy.
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PMID:Comparative effects of pirenzepine and cimetidine, alone and in combination, on 24-hour gastric acidity in duodenal ulcer disease. 639 32

The stereochemistry and the dynamics of two loops of yeast tRNA-asp, the thymine loop and the anticodon loop, are compared in the hope of a better understanding of the relationships between loop sequence and loop topology. Both loops are seven residues long and both present sharp turns after the second residue, U33 and psi 55, stabilized by hydrogen bonds between N3-H of the pyrimidine and the phosphates of C36 and A58 and stacking interactions of the pyrimidine ring with the phosphates of U35 and A57, respectively. In the thymine loop, the two purines following C56, A57 and A58, open up to leave space for the intercalation of the first invariant guanine residue of the D-loop, while the two pyrimidine bases, which follow A58, turn away from the stacking pattern of the thymine arm and stack instead with the last base pair of the dihydrouridine arm A15-U48. In the anticodon loop, however, the bases G34 to C38 form an helical stack in continuity with the anticodon stem on the 3'-end. At the same time C36 forms Watson-Crick hydrogen bonds with G34 of a twofold symmetrically related molecule. The anticodon-anticodon base pairing interactions between symmetrically-related molecules are stabilized by stacking with the modified base G37 on both sides of the triplet. Some comparisons are made with the structure of yeast tRNA-phe and some implications about the structure of mitochondrial tRNAs are discussed.
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PMID:Loop stereochemistry and dynamics in transfer RNA. 640 Nov 14

Vagal stimulation by modified shamfeeding in healthy subjects induced about fourfold increases of gastric outputs of acid, chloride, sodium and potassium. Prior oral 15(R)15 methyl prostaglandin E2 inhibited dose-dependently the peak and total gastric acid response to modified shamfeeding by lowering both the secreted volumes and the acidity. The inhibition by 15 micrograms of the analogue exceeded 50% and the suppression was submaximal by 140 micrograms. Gastric output of chlorides decreased in a dose-related way. The hydrogen ion output was proportionally more reduced than the chlorides. The analogue did not affect the gastric output of sodium. Potassium decreased in a dose-related way. Indomethacin was without effect on the gastric acid response to shamfeeding but reduced the sodium output compared to in controls and in series with the analogue. Plasma gastrin was slightly but significantly elevated by the shamfeeding procedure. This elevation was absent or even reversed by 15(R)15 Me PGE2. No effect was recorded by indomethacin pretreatment. Vagal stimulation augments both the parietal and non-parietal components of the gastric secretion. Low doses of oral 15(R)15 Me PGE2 were effective in suppressing the vagally stimulated acid secretion. Neutralization by the gastric non-parietal secretion can contribute to reduce the acid response. Blocking of the prostaglandin biosynthesis decreased gastric sodium output, suggesting indirectly that endogenous prostaglandins may be involved in modulating the gastric non-parietal secretion.
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PMID:Effect of graded 15(R)15 methyl prostaglandin E2 and of indomethacin on the gastric secretory and plasma gastrin response to modified shamfeeding. 651 89

Measurements of gastric pH and hydrogen ion concentration were made serially for six hours in five rhesus monkeys. Both pH and hydrogen ion concentration showed rapid fluctuations with periods approximating 90 minutes. These rhythms persisted in the face of continuous infusion with Pentagastrin, indicating that while gastrin release is sufficient to stimulate acid secretion, it is not the only mechanism of acid control.
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PMID:Ultradian rhythms of gastric acidity. 670 1

A modified magnesium hydrogen breath test, using end expiratory breath sampling, is described to investigate achlorhydria. The efficacy of this test in the diagnostic investigation of pernicious anaemia was compared with that of serum pepsinogen I. Twenty one patients with pernicious anaemia--that is, patients with achlorhydria--and 22 with healed duodenal ulcer and normal chlorhydria were studied. Magnesium hydrogen breath test, serum pepsinogen I, serum gastrin, and standard gastric acid secretory tests were performed in all subjects. The mean (SEM) hydrogen peak value was lower in patients with pernicious anaemia than in the duodenal ulcer group (21.7 (1.9) v 71.3 (5.2) ppm; p = 0.00005). The hydrogen peak value had a 95.2% sensitivity and a 100% specificity to detect pentagastrin resistant achlorhydria. Mean serum pepsinogen I concentrations were also significantly lower in patients with pernicious anaemia than in the duodenal ulcer group (10.7 (2.7) v 123.6 (11.8) micrograms/l p = 0.00005). Sensitivity and specificity to detect pernicious anaemia were both 100% for pepsinogen I. It is concluded that this modified magnesium hydrogen breath test is a simple, noninvasive, cost effective, and accurate method to assess achlorhydria and may be useful in the diagnostic investigation of patients with suspected pernicious anaemia.
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PMID:Magnesium hydrogen breath test using end expiratory sampling to assess achlorhydria in pernicious anaemia patients. 795 24


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