Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To assess the physiologic significance of tyrosine o-sulfation of gastrin in humans, the gastric acid stimulatory potencies of sulfated and non-sulfated human gastrin-17 were compared in six normal young subjects. Sulfated and non-sulfated forms of synthetic human gastrin-17 were infused intravenously in doses from 12.7 to 478 pmol/kg/h. Similar acid secretory responses were observed. The calculated maximal acid response for sulfated gastrin-17 was 35.7 +/- 4.3 mmol/h, and that for non-sulfated gastrin-17 was 39.8 +/- 7.5 mmol/h (mean +/- SEM, NS). The 50% effective dose of sulfated gastrin-17 was 22.2 +/- 6.7 pmol/kg/h, whereas it was 29.3 +/- 5.8 pmol/kg/h for non-sulfated gastrin-17 (NS). Finally, the 50% effective concentration of gastrin in serum was 34.7 +/- 5.0 pmol sulfated gastrin-17/l and 42.5 +/- 11.8 pmol non-sulfated gastrin-17/l (NS). The results show that tyrosine o-sulfation is without significant influence on the gastric acid secretory potency of gastrin in man. Moreover, the results also suggest that sulfated and non-sulfated gastrin-17 in man have similar rates of metabolism.
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PMID:Does sulfation of gastrin influence gastric acid secretion in man? 239 89

In a double-blind placebo-controlled study, we examined the effect of calcitonin on gastric emptying, and on serum concentrations of gastrin, insulin, glucose, calcium, and phosphorus after a mixed solid-liquid meal in 11 healthy men. Synthetic salmon calcitonin was administered as a 415 pmol i.v. bolus injection followed by a 90-min infusion to reach an overall dose of 62.25 pmol/kg body mass. Gastric emptying of a radiolabeled meal was surveyed by means of a gamma camera. A pronounced inhibition of gastric emptying with calcitonin was observed in all subjects (median gastric half emptying time 60.3 min after placebo versus 197.6 min after calcitonin; p less than 0.001). Calcitonin did not effect the postprandial gastrin release, nor did it change significantly the serum calcium or phosphorus concentrations. A decreased postprandial insulin release by calcitonin (mean +/- SEM area under the insulin curve 2,124.6 +/- 382.0 min mU L-1 after placebo versus 640.9 +/- 124.0 min mU L-1 after calcitonin; p less than 0.002) was accompanied by a different pattern of serum glucose concentrations during the infusion of the hormone when compared to the situation with a placebo. We discuss potential mechanisms and clinical relevance of our findings.
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PMID:Effect of calcitonin on gastric emptying and on serum insulin and gastrin concentrations after ingestion of a mixed solid-liquid meal in humans. 240 30

Somatostatin is known to inhibit hormone release and gastrointestinal secretion and hence may be useful in the treatment of amine precursor uptake, decarboxylase tumors. Clinical application has been limited by the short half-life, potency, and specificity of the natural hormone. Our study evaluated the effect of a synthetic analog of somatostatin, SMS 201-995 (Sandoz, Inc., E. Hanover, N.J.) on basal and stimulated gastrin release and gastric acid secretion in 10 patients with the Zollinger-Ellison syndrome. In experiment 1, H2-receptor antagonists were discontinued for 48 hours; SMS 201-995, 1 microgram/kg, was given subcutaneously; gastrin and SMS levels in plasma were determined by radioimmunoassay; and gastric secretion was measured and titrated at 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, and 18 hours. The mean +/- SEM baseline gastrin level (1526 +/- 733 pg/ml) was significantly inhibited for 16 hours (p less than 0.05, paired t test). Gastric secretion was neutralized for as long as 18 hours (p 0.05). In experiment 2, three patients received either a secretin (2 U/kg) or a calcium stimulation test (2 mg/kg) with or without pretreatment with SMS 201-995, 1 microgram/kg, subcutaneously. The mean +/- SEM interpreted change in gastrin (ng X 60 min/ml) without SMS 201-995, 36.8 +/- 11 (secretin), and 129 +/- 30 (calcium) were reduced with SMS 201-995 to -1.1 +/- 0.76 (secretin) and -29 +/- 28 (calcium) (p less than 0.05). In the Zollinger-Ellison syndrome, SMS 201-995 caused significant and long-lasting inhibition of both tumor gastrin release and gastric acid secretion, probably by direct action on both the gastrinoma and the stomach. SMS 201-995 blocks acid secretion and secretin- and calcium-stimulated gastrin release, indicating that SMS 201-995 inhibits peptide secretion by postreceptor mechanisms. SMS 201-995 will be useful in the palliative treatment of apudomas.
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PMID:Observations on the effect of a somatostatin analog in the Zollinger-Ellison syndrome: implications for the treatment of apudomas. 242 19

The effect of the H2 agonist impromidine, gastrin 1-17 (G1-17), pentagastrin, and the M1 agonist McN-A-343 on pepsin secretion in the acid-inhibited totally isolated, vascularly perfused rat stomach was studied. Omeprazole produced a 97-98% inhibition of stimulated acid outputs. Base-line pepsin output after omeprazole was 712 +/- 278 micrograms/h (mean +/- SEM) and, after stimulation with impromidine, 1528 +/- 164 micrograms/h; G1-17, 1520 +/- 180 micrograms/h; and pentagastrin, 2063 +/- 605 micrograms/h. Output after McN-A-343 was 534 +/- 69 micrograms/h. Pepsin secretion after impromidine, G1-17, and pentagastrin was significantly (p less than 0.01) higher than base-line output. McN-A-343 had no significant effect on pepsin output in this model. Pepsin secretion after impromidine, G1-17, and pentagastrin was considerably lower than found in the same model with uninhibited acid output. This could be caused by decreased tubular 'washout' after acid inhibition, and, accordingly, no conclusions can be drawn as to the possible stimulatory effect of acid on pepsin secretion. However, the present study indicates that pepsin secretion can be stimulated directly by impromidine and (penta)gastrin without concomitant acidification of the gastric glands.
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PMID:Stimulated pepsin secretion after omeprazole-induced acid suppression in the totally isolated, vascularly perfused rat stomach. 243 47

Increasing doses of gastrin 1-17 (G1-17) were administered to totally isolated, vascularly perfused rat stomachs prestimulated with the phosphodiesterase inhibitor isobutyl methylxanthine (IMX). Vascular and luminal histamine outputs and luminal acid output were monitored at short intervals. G1-17 induced an immediate histamine release to the vascular perfusate, preceding the increase in acid secretion by approximately 10 min. Vascular histamine output increased from a base line (IMX only) of 4.0 +/- 0.4 to a maximum of 34.5 +/- 7.3 nmol/60 min (mean +/- SEM) after 1040 pM G1-17, and acid output from 8.0 +/- 2.8 to 61.5 +/- 7.0 mumol/60 min after 520 pM G1-17. Acid output was correlated to vascular histamine release (r = 0.64, p less than 0.001). Gastrin produced a histamine release giving gastric venous concentrations of the same magnitude as the concentration of histamine necessary to induce a comparable acid response. Histamine release to the lumen, on the other hand, paralleled the acid secretion in time, suggesting it to be a passive phenomenon secondary to acid secretion. Thus, the present study for the first time shows that gastrin induces vascular histamine release of such a magnitude that this substance could be the mediator of the gastrin effect on acid secretion.
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PMID:Gastrin produces an immediate and dose-dependent histamine release preceding acid secretion in the totally isolated, vascularly perfused rat stomach. 244 18

The effects of the prostaglandin E1 analogue misoprostol on base-line and stimulated (gastrin, histamine, and the muscarinic M1 agonist McN-A-343) acid secretion, base-line and gastrin-stimulated histamine release, and base-line and McN-A-343-stimulated gastrin release in the totally isolated, vascularly perfused rat stomach were studied. At a concentration of 1 nM, misoprostol significantly (p less than 0.01) inhibited base-line acid secretion from 13.7 +/- 2.7 to 4.8 +/- 0.7 mumol/60 min, histamine-stimulated acid secretion from 99.9 +/- 15.1 to 21.8 +/- 8.2 mumol/60 min, maximal gastrin-stimulated secretion from 92.5 +/- 11.4 to 3.1 +/- 0.6 mumol/60 min, and maximal McN-A-343-stimulated secretion from 60.0 +/- 8.9 to 6.8 +/- 2.6 mumol/60 min (mean +/- SEM). Likewise, misoprostol significantly inhibited base-line vascular histamine release (p less than 0.05) from 10.1 +/- 2.3 to 3.7 +/- 0.7 nmol/60 min and gastrin-stimulated release (p less than 0.01) from 54.7 +/- 7.9 to 20.2 +/- 4.1 nmol/60 min (mean +/- SEM). The gastrin release was not affected by misoprostol. We conclude that misoprostol inhibits acid secretion both by a direct effect on the parietal cell and by inhibiting endogenous histamine release.
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PMID:The effect of misoprostol on base-line and stimulated acid secretion and on gastrin and histamine release in the totally isolated, vascularly perfused rat stomach. 245 56

Hypoacidity and hypergastrinaemia have been reported in the newborn human. However, little is known about in utero gastric acid secretion, and the relationship to fetal plasma gastrin levels. The longitudinal pattern of development of basal and stimulated gastric acid secretion in the non-anaesthetized fetal sheep has been studied during the last 45 days of gestation. Fetuses had cannulae inserted into the jugular vein, carotid artery and stomach. Gastric juice and blood was sampled daily from 101 days gestation until birth (145 days). Intermittent basal acid secretion began between 120 and 133 days of gestation. These fluctuations in gastric juice pH continued until birth. Overall there was a decline in gastric pH from 7.5 +/- 0.2 (SEM), for fetuses 101-105 days to 4.3 +/- 0.5 by 131-135 days. Mean fetal plasma gastrin was higher than maternal levels after 111-115 days but no correlation between fetal plasma gastrin levels and gastric pH could be demonstrated. Pentagastrin and histamine infusion did not stimulate acid secretion in fetuses younger than 115 days. After this age the fetuses became responsive to both pentagastrin and histamine. In contrast, cholinergic stimulation, using bethanechol, did not stimulate acid production until 10 to 15 days later, suggesting a hierarchy in the development of the control of acid secretion in the fetus. The lack of response to endogenous gastrin and the hierarchy in the control of acid secretion suggest either a lack of receptors on the parietal cell or the presence of an inhibitor of acid secretion. These studies are relevant to human physiology since the present findings show that the sheep and human have a similar gastrin/acid profile at birth.
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PMID:Ontogeny of gastric acidity in the ovine fetus. 286 Dec 25

Specific somatostatin (SRIH) receptors on human pituitary adenoma cell membranes were characterized using [125I]Tyr11-SRIH as the radioligand. Specific binding of [125I] Tyr11-SRIH to adenoma cell membranes reached a steady state within 30 min at 25 C, and semilogarithmic analysis of the data revealed that the rate of the binding was linear at 25 C with a t1/2 of 13.2 min. Specific binding increased linearly with 5-160 micrograms plasma membrane protein. SRIH-14 and SRIH-28 inhibited [125I]Tyr11-SRIH binding to adenoma cell membranes with ID50S of 0.32 and 0.50 nM, respectively, while secretin, glucagon, gastrin, cholecystokinin-8, bombesin, TRH, LHRH, human GH-releasing factor-(1-44)-NH2, D-Ala2-met-enkephalin, gamma-aminobutyric acid and taurine did not significantly inhibit binding. All of 13 GH-secreting adenomas investigated had specific and high affinity SRIH receptors, with a dissociation constant (Kd) of 0.80 +/- 0.15 nM (mean +/- SEM) and a maximal binding capacity (Bmax) of 234.2 +/- 86.9 fmol/mg protein (mean +/- SEM). Among five of the nonsecreting pituitary adenomas examined, two had SRIH receptors with Kd values of 0.18 and 0.32 nM and Bmax values of 17.2 and 48.0 fmol/mg protein, respectively. In the remaining three, SRIH receptors were not detected. These results indicate that GH-secreting adenomas as well as some nonfunctioning adenomas have specific SRIH receptors, and hence, the function of the adenomas could be altered by SRIH.
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PMID:Specific somatostatin receptors on human pituitary adenoma cell membranes. 286 81

The present study intended to investigate the effect of antroduodenal acidification on gastric acid secretion and emptying, gastrin and somatostatin release in response to food in healthy subjects as well as in duodenal ulcer patients. Ten duodenal ulcer patients and 9 normal controls were studied twice: the same 400 ml liquid protein meal (proteins: 10 g) was introduced into the stomach; then intragastric pH was either maintained at pH 4.5 or allowed to decrease in response to the meal. Acid secretion was calculated using the intragastric titration method (for which the intragastric pH is fixed at pH 4.5) and using the serial dilution indicator method (which allows antral acidification) respectively. Gastric emptying was estimated according to: a) iterative measurements of intragastric meal residual volume; b) volume passing through the pylorus. These two tests were performed in a random order and during each, plasma gastrin and somatostatin responses to the meal were determined. In healthy subjects, antral acidification following the meal was associated with a significantly lower acid secretion (17.3 +/- 0.9 mmol/h; m +/- SEM) than when the pH was maintained at pH 4.5 (20.2 +/- 1.3; p less than 0.05). Moreover, gastric emptying was slower when the pH was allowed to decrease (t 1/2: 26.2 +/- 1.4 min) than when the pH was constant (t 1/2: 20.5 +/- 2.2 min; p less than 0.05). By contrast, in the duodenal ulcer group, neither acid output nor gastric emptying were significantly different in the two situations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Consequences of antral and duodenal acidification on acid secretion, gastrin response and gastric emptying in duodenal ulcer patients and normal subjects]. 287 1

Forty-six patients with the gastrinoma syndrome were divided into 2 categories: 1) benign sporadic gastrinoma (n = 30), and 2) gastrinoma with metastases to liver (n = 16). Thirteen of the 46 patients had multiple endocrine neoplasia type I syndrome. Serum gastrin levels in patients fasted overnight were determined by RIA using antisera directed toward the NH2- and COOH-terminals of heptadecapeptide gastrin (G17) and the NH2-terminus of the triacontatetrapeptide (G34). These results were compared with findings in 50 normal subjects. In the normal subjects, the mean COOH-terminal gastrin-17 level was higher [65 +/- 8 (+/- SEM) pg/ml] than the NH2-terminal gastrin-17 level (11 +/- 0.2 pg/ml) and lower than the NH2-terminal gastrin-34 level (134 +/- 20 pg/ml). The levels of NH2-terminal gastrin-17 were higher in patients with metastatic disease than in those with benign gastrinoma, whereas the COOH-terminal gastrin-17 and the NH2-terminal gastrin-34 levels were similarly high in both groups. The mean ratio of NH2-terminal gastrin-17 to COOH-terminal gastrin-17 was less than 1 in normal subjects (0.22 +/- 0.02) and benign gastrinoma patients (0.2 +/- 0.04), and it was 2.2 +/- 0.41 in the patients with metastatic gastrinoma. An NH2 to COOH gastrin-17 ratio greater than 1 was found in 13 of 16 patients with metastatic gastrinoma, but in none of the patients with benign gastrinoma or normal subjects. Similar results were found in multiple endocrine neoplasia type I patients with benign and metastatic disease. A high NH2 to COOH gastrin-17 ratio is suggestive of metastatic gastrinoma. In 4 patients with metastatic gastrinoma, the NH2 to COOH gastrin-17 ratio fell in parallel with the response to chemotherapy.
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PMID:Evaluation of NH2-terminus gastrins in gastrinoma syndrome. 287 76


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