Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine possible sites and mechanisms of action of somatostatin (SS) in gastric secretory mucosa, secretion of pepsin, H+, Cl-, Na+ and K+ was stimulated in conscious fistula dogs by i.v. infusion of bethanechol, pentagastrin and histamine in the absence and presence of SS-14. At low dose (0.5 micrograms or 300 pmol/kg/h), SS-14 potently inhibited H+ and pepsin stimulated by bethanechol (80 micrograms/kg/h) to less than 5% of control; it required 2 micrograms or 1200 pmol/kg/h of SS-14 to achieve similar inhibition of pentagastrin (1.5 micrograms/kg/h)-stimulated secretion. In both cases, gastric [K+] was depressed by SS-14 infusion and recovered before H+ and pepsin. Similar sensitivity to SS suggests a Ca++-dependent mechanism or pathway of stimulation by gastrin similar to that by cholinergic agonists. By contrast, histamine, which acts via cyclic AMP pathways, was not inhibited by a large dose of SS-14 (20 micrograms/kg/h). SS inhibition is thus agonist (or pathway)- rather than organ- or cell-specific.
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PMID:Somatostatin effects on gastric electrolytes and pepsin in dogs with various secretory stimuli. 289 Jul 56

In vivo secretion of gastric acid and pepsin has been studied in pylorus-ligated cod. Basal acid output amounted to 100-150 mumol H+.kg-1.h-1 and pepsin secretion to 1 mg.kg-1.h-1. In response to bombesin nonapeptide (2.4 nmol.kg-1.h-1) and histamine (81 nmol.kg-1.h-1), acid secretion increased to approximately 200 and 600% of the basal level, respectively. Pepsin output was marginally affected by histamine but increased to approximately 3 and 15 times the basal level during treatment with bombesin and eledoisin (3.27 nmol.kg-1.h-1). Somatostatin (SS-14, 15 nmol.kg-1.h-1) inhibited basal acid secretion by 85%. It also inhibited the acid secretion during stimulation with bombesin (68%) and histamine (57%), but although the former effect could be explained by removal of the basal component, the latter could not. Basal pepsin secretion was not affected by SS-14. A slight inhibition (28%) of the peak pepsin response to eledoisin was demonstrated, and bombesin failed to stimulate pepsin secretion during treatment with SS-14. These results indicate that endogenous somatostatin, if present in the cod stomach, could play a role in the regulation of gastric secretion.
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PMID:Effect of somatostatin on basal and stimulated gastric secretion in the cod, Gadus morhua. 289 72

CHAPTER 1. The gastric functions are regulated in a complex manner by the autonomic nervous system, sympathetic and parasympathetic, and hormones and moreover by a system of peptide-containing cells and nerves. The sympathetic influence is mediated by alpha- and beta-adrenoceptors, beta-adrenoceptor agonists in general inhibit the gastric functions. The effects of the beta-adrenoceptors are probably mediated indirectly, and the responsible mechanism may be via release of and endogenous mediator--somatostatin or serotonin. The purpose of the present study, described in the survey, is to examine whether somatostatin or serotonin acts as a mediator for the gastric effects in vivo of beta-adrenoceptor agonists. The proposed mediator must present the following characteristics: A. Inhibitory effects of "physiological" doses in vivo. B. Inhibitory characteristics similar to those of the beta-adrenoceptor agonists. C. A beta-adrenoceptor mediated release. CHAPTER 2. In this chapter the known effects of beta-adrenoceptor agonists on gastric functions (acid secretion, pepsin secretion, antral motility and mucosal blood flow) are presented. The possible mechanisms mediating these effects are mentioned, and the effects of somatostatin and serotonin are reviewed. Beta-adrenoceptor agonists inhibit the acid secretion in vivo in several species, but stimulate in vitro. A similar pattern is probable as for the pepsin secretion, but sufficient results are not available in order to draw a certain conclusion. The antral motility is inhibited both in vivo and in vitro. The mucosal blood flow is increased compared to the acid secretion, however the results points to variable effects depending on the circumstances of the experiments. On the basis of the reviewed effects of somatostatin it is concluded that the effects are inhibitory, but the inhibitory characteristics are not known. A beta-adrenoceptor mediated release of somatostatin has been found, but it has not been examined selectively for the stomach. The gastric effects of serotonin has been sparsely examined and it is not possible to determine the effects as parts of a certain characteristic. It is concluded that neither somatostatin nor serotonin have been examined sufficiently to determine which is the proposed mediator. CHAPTER 3. The materials and methods used are reviewed. Dogs were used and various parameters were measured--acid secretion by titration, pepsin secretion by enzymatic process with haemoglobin as substrate, antral motility by registration of intraluminal pressure, mucosal blood flow by the clearance of neutral red, somatostatin by radioimmunoassay.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The role of somatostatin and serotonin in the beta-adrenoceptor regulation of gastric function. An experimental study in dogs. 289 1

The actions of progressive doses of intraperitoneally (IP) administered somatostatin-14 (SS-14) and -28 (SS-28) on gastric secretion (acid, pepsin) and mucosal blood flow (MBF) were studied in conscious gastric fistula rats both under basal conditions and under additional administration of pentagastrin. Also, somatostatin-like immunoreactivity was measured in aortal blood in all groups as well as aortal gastrin levels under basal conditions. IP infusion of equimolar doses of SS-14 and SS-28 resulted in an equal and dose-dependent inhibition of basal as well as pentagastrin-stimulated gastric acid secretion. MBF was reduced by either peptide both in the basal and pentagastrin experiments. Under basal conditions pepsin secretion was significantly increased by infusion of SS-14 at the higher doses, by infusion of SS-28 only at the intermediate dose (3.1 nmole kg-1.hr-1). In the pentagastrin experiments, low and intermediate doses of SS-14 tended to lower pepsin outputs but the highest dose of SS-14 stimulated pepsin secretion, whereas SS-28 had no effect on pepsin. Administration of SS-28 inhibited gastrin only at the highest dose (12.3 nmole kg-1.hr-1), and SS-14 had no influence at all on gastrin. After IP infusion of both peptides, plasma SLI rose dose-dependently under basal and stimulated conditions. Gel chromatography indicated an in-vivo conversion of SS-28 to SS-14 or intermediate fragments. It is concluded that SS-14 and SS-28 delivered by IP infusion, inhibit basal and stimulated gastric acid equally in the rat without suppressing gastrin. The mechanism underlying SS-mediated pepsin stimulation is unknown.
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PMID:Gastric secretion and gastrin under progressive doses of somatostatin-14 and -28 administered intraperitoneally to the rat. 289 78

Measurements of acid and pepsin secretions and of histamine release in response to food alone or in combination with graded doses of antramine (AH), a molecular form of histamine isolated from antral mucosa, with or without somatostatin were performed simultaneously in dogs equipped with a denervated pouch. AH restored somatostatin-inhibited acid and pepsin secretions but with different intensities in regard to the different inhibitory levels induced by somatostatin. AH competitively antagonized somatostatin (1 microgram/kg/h) inhibition of acid secretion, but when stronger levels of inhibition were achieved, AH restored weakly acid secretion. Recovery of pepsin secretion occurred through a competitive mechanism between AH and somatostatin (1 and 2 micrograms/kg/h). There was a close relationship between the secretory outputs and the integrated histamine responses; the slopes of the regression lines might be considered as reflecting the stimulatory activity of blood histamine on secreting cells. For acid secretion, this activity is similar in control and somatostatin (1 microgram/kg/h) tests, while for pepsin secretion it is identical in control and 1 or 2 micrograms/kg/h somatostatin tests. One can speculate that the suppression of the somatostatin inhibitory effects by antramine, within the limits of physiological conditions, results from a competitive mechanism.
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PMID:The somatostatin/histaminic pathway balance on gastric secretion could be based on a competitive antagonism. 290 61

40749 RP, a pyridyl-2-tetrahydrothiophene derivative, is known to be a potent inhibitor of the gastric acid response to pentagastrin, betazole and a meal. In 6 healthy young volunteers, a single oral dose of 2 mg.kg-1 greatly reduced the gastric acid secretory response to sham-feeding. By contrast, neither gastric pepsin nor the plasma PP response were altered by the drug. No change was observed in plasma gastrin, motilin, VIP or somatostatin concentrations. The results show that 40749 RP is also active on the pure vagus-stimulated gastric acid secretion. The lack of effect upon gastric pepsin and plasma PP suggests that 40749 RP is not likely to act on the basolateral cholinergic receptor and that it affects further cellular steps involved in hydrogen ion secretion.
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PMID:Effect of 40749 RP on basal and sham feeding stimulated gastric secretion in man. 312 55

Somatostatin (SS) has been reported to exert potent inhibitory effects on gastric acid, pepsin and gastrin secretion. Although still controversial, the results of several studies have shown a possible influence of a local decrease in gastric somatostatin in the physiopathologic characteristics of peptic ulcer disease. In the present study, immunoreactive SS content (SLI) of antral (SLI-a), corpal (SLI-c) and fundic (SLI-f) mucosal extracts was measured by radioimmunoassay (RIA) in control patients (C) and in those patients with duodenal ulcer (DU) or gastric ulcer (GU) to further study a possible role of SS in peptic ulcer disease. Fifty-five patients (C = 20, DU = 21 and GU = 14) were included in the study. Gastric mucosal samples were obtained either by endoscopic biopsy (4.6 +/- 0.2 milligrams of weight) or operation (52.3 +/- 3.8 milligrams of weight). RIA was performed after a modified Arimura's method and results were expressed as nanograms per milligram of tissue plus or minus standard error of the mean. Chromatographic analysis of gastric mucosal extracts was performed on a Sephadex G-25 fine column. A great interindividual variation in SLI levels was observed (a range of 0.02 to 5.30 nanograms per milligram of weight). The mean SLI concentrations were: C (SLI-a, 2.55 +/- 0.45, SLI-c, 0.99 +/- 0.46 and SLI-f, 1.03 +/- 0.21); DU (SLI-a, 0.48 +/- 0.16, SLI-c, 0.43 +/- 0.13, and SLI-f, 0.58 +/- 0.12), and GU (SLI-a, 1.10 +/- 0.25, SLI-c, 0.40 +/- 0.10, and SLI-f, 0.81 +/- 0.24). Significantly greater amounts of SLI contents were found in the antrum of control patients as compared with those found in the corpus or fundus (p less than 0.05 and p less than 0.01, respectively). SLI-a levels were lower in peptic ulcer patients (DU, p less than 0.001 and GU, p less than 0.05) than in control patients. There was also a significant difference between SLI-a levels in DU versus GU patients (p less than 0.05). No significant differences were found in SLI-c and SLI-f contents in all three groups studied. In conclusion, these results suggest that decreased SS levels in antral gastric mucosa could be the alteration underlying the various physiopathologic mechanisms involved in the development of peptic ulcer disease.
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PMID:Gastric mucosal somatostatin-like immunoreactivity in peptic ulcer. 356 43

Large increases in gastric acid and pepsin secretion, antral gastrin concentration, and decreases in serum gastrin occur during the third week of life in the neonatal rat. At the same time gastrin receptors appear and gastrin release becomes sensitive to somatostatin, indicating that absence and then appearance of specific hormone receptors may be responsible for some of the ontogenic pattern. At this time the mucosa also begins to grow rapidly, with a greater proportion of cells leaving the proliferative pool and differentiating. For the first 2.5-3 weeks these ontogenic changes can be triggered by corticosterone. Their full expression depends on dietary changes associated with weaning. Neither hormones, dietary changes, nor the weaning process itself is essential for development, because in the absence of these, all of the changes still occur--although they may be delayed or be smaller in magnitude. Figure 1 provides a generalized summary of the normal functional development of the stomach and how it is altered by changes in corticosterone levels and the absence of weaning. These findings indicate that ontogeny is genetically programmed and that the full expression of this program depends on hormones, luminal contents, and other environmental factors. In comparison with the small intestine, for example, gastric ontogeny has not received adequate attention. There are essentially no studies directed toward understanding changes in motility during this period. There is really only one study examining the growth pattern of the mucosa during development, and this study is aimed at changes in DNA synthesis and cell loss. Experiments involving the cell cycle are needed to understand whether existing cells mature and differentiate or whether newly created cells suddenly leave the proliferative pool to differentiate. There have been no experiments in which the effects of thyroid hormone on gastric development have been adequately examined. In addition, little or nothing is known about EGF in the ontogenic process. Studies implanting fetal tissue into adult hosts are needed to determine which gastric functions can develop in the absence of luminal stimulation and hormone changes. The cell biology of the gastric mucosa is difficult to examine--especially that involving the cells concerned with growth and differentiation. The stem cells are dispersed throughout the tissue and are a small portion of the cell population. These have never been isolated for study. In vitro culture of mucosal cells, however, is a technique that can possibly be used to examine development at the cellular and molecular level.
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PMID:Functional development of the stomach. 392 87

SSeven new analogues of somatostatin are described, along with the effects of these analogues on pentagastrin-stimulated gastric acid and pepsin secretion in conscious cats. Replacement of the cystine disulphide bridge of somatostatin with an amide bridge, with or without deletion of the N-terminal dipeptide, resulted in analogues with approximately 20% of the potency of somatostatin. Simultaneous ommision of Lys4 in the amide-bridge analogues reduced the activity of the peptides to approximately 5% of somatostatin. Substitution of Phe6 of somatostatin or an amide-bridged analogue with azaphenylalanyl resulted in peptides with no detectable activity. The results illustrate the possible importance of the basic side-chain of Lys4 for the activity of somatostatin. The lack of activity of azaphenylalanyl6 analogues of somatostatin demonstrate the extreme importance of the orientation of the side-chain of Phe6 for the activity of somatostatin, possibly for the binding to somatostatin receptors.
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PMID:Non-reducible cyclic, and azaphenylalanyl6 analogues of somatostatin. 610 84

Six healthy young males were studied with an intravenous infusion of saline for 1 h, followed by somatostatin, 100 microgram/h, for 2 h, and thereafter by another 2 h with saline infusion. Gastric H+ and pepsin outputs were determined in 30-min periods throughout the study. Blood was drawn at regular intervals, and blood glucose was determined by a hexokinase method. PG I and gastrin in serum were determined by radioimmunoassay methods. Gastric H+ and pepsin outputs were markedly reduced during the somatostatin infusion and the first 30-min period after cessation of the somatostatin infusion. In the subsequent 60-min period gastric pepsin secretion increased significantly as compared with the basal period, whereas the gastric H+ output only increased non-significantly. Mean serum PG I increased during the somatostatin infusion and remained elevated throughout the study. The rise in serum PG I was marked in five and only marginal in the sixth person. Serum gastrin fell during the somatostation infusion and returned to the basal level thereafter. Blood glucose, on the other hand, fell only during the first 90 min of somatostatin infusion, and then climbed to the basal level, where it stayed for the remaining part of the study. The present results suggest that the pepsinogen synthesis is unaffected by somatostatin, and that serum PG I seems to reflect the amount of pepsinogens stored in the gastric mucosa.
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PMID:The effect of somatostatin on serum group I pepsinogens (PG I), serum gastrin, and gastric H+ and pepsin secretion in man. 610 88


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