Studies on the inhibition of pancreatic secretion by luminal somatostatin

1981 ◽  
Vol 241 (2) ◽  
pp. G109-G115 ◽  
Author(s):  
S. J. Konturek ◽  
J. Tasler ◽  
M. Cieszkowski ◽  
J. Jaworek ◽  
A. Arimura ◽  
...  
Keyword(s):  
Pancreatic Secretion ◽  
Exocrine Pancreas ◽  
Inhibitory Action ◽  
Serum Gastrin ◽  
Gastrointestinal Hormones ◽  
Duodenal Mucosa ◽  
Enzyme Protein ◽  
Duodenal Acidification ◽  
Pancreatic Fistulas ◽  
Stimulation Of

The effects of somatostatin, instilled into the duodenum or administered intravenously, on pancreatic response to endogenous (meal and duodenal acidification) or exogenous (secretin and caerulein) stimulants were compared in five dogs with gastric and pancreatic fistulas. Somatostatin, whether applied topically to the duodenal mucosa or given intravenously, resulted in qualitatively similar inhibition of pancreatic secretion of water, bicarbonate, and enzyme protein, being about four to eight times less potent after intraduodenal than after intravenous administration. A meal-induced secretion appears to be the most sensitive to the inhibitory action of intraduodenal somatostatin, probably because of the suppression of gastric acid and serum gastrin secretin involved in the postprandial stimulation of the exocrine pancreas. The inhibition of pancreatic secretion by luminal somatostatin was accompanied by a significant increase of plasma levels of the immunoreactive somatostatin, indicating that this peptide can be absorbed intact across the intestinal mucosa. We conclude that somatostatin administered into the gut lumen is absorbed into the circulation and can inhibit pancreatic secretion both by the suppression of the release of gastrointestinal hormones and by direct inhibitory action on the exocrine pancreas.

Comparison of effects of neurotensin and fat on pancreatic stimulation in dogs

1983 ◽  
Vol 244 (6) ◽  
pp. G590-G598 ◽  
Author(s):  
S. J. Konturek ◽  
J. Jaworek ◽  
M. Cieszkowski ◽  
W. Pawlik ◽  
J. Kania ◽  
...  
Keyword(s):  
Protein Secretion ◽  
Pancreatic Secretion ◽  
General Circulation ◽  
Constant Ph ◽  
Equal Rate ◽  
Duodenal Acidification ◽  
Pancreatic Fistulas ◽  
Protein Response ◽  
Dose Dependent ◽  
Stimulation Of

In six conscious dogs with esophageal, gastric, and pancreatic fistulas, the effects of intravenous infusion of neurotensin and intraduodenal instillation of sodium oleate on gastric and pancreatic secretion were determined under basal conditions and after exogenous (secretin and cholecystokinin octapeptides) or endogenous stimulants (feeding and duodenal acidification). Neurotensin given intravenously in graded doses (1.5–200 pmol . kg-1 . min-1) to fasted dogs produced a dose-dependent stimulation of pancreatic bicarbonate and protein secretion reaching, respectively, about 18 and 100% of maximal responses to secretin and cholecystokinin octapeptide (CCK). Duodenal oleate in graded doses (0.5–16 mmol/h) resulted in a similar pattern of bicarbonate and protein secretion but increased plasma neurotensin only to about 10% of that achieved with infusion of exogenous neurotensin producing an equal rate of pancreatic secretion. Neurotensin, like oleate, potentiated the action of secretin and CCK on pancreatic bicarbonate and had additive effects on protein response to these secretagogues. Both neurotensin and oleate increased pancreatic response to liver extract meal kept in the stomach at constant pH (5.5) and the response to sham feeding but decreased the response to ordinary feeding, probably due to the inhibition of gastric acid secretion and reduction of duodenal acidification. Neurotensin given intra-arterially directly to the pancreas or to isolated intestinal segment increased dose dependently the blood flow and oxygen consumption without affecting general circulation. We conclude that 1) neurotensin mimics the pancreatic secretory effects of intestinal fat, 2) neurotensin may contribute in part to fat-induced stimulation of the pancreatic secretion, and 3) the secretory effects of neurotensin are accompanied by a marked stimulation of intestinal and pancreatic circulation and metabolism.

Stimulation of mucosal growth by a dietary amine

1984 ◽  
Vol 247 (4) ◽  
pp. G352-G356 ◽  
Author(s):  
A. B. Dembinski ◽  
T. Yamaguchi ◽  
L. R. Johnson
Keyword(s):  
Protein Content ◽  
Serum Gastrin ◽  
Duodenal Mucosa ◽  
Proximal Colon ◽  
Gastrointestinal Mucosa ◽  
Trophic Effect ◽  
Oxyntic Gland ◽  
Mucosal Growth ◽  
Normal Constituent ◽  
Stimulation Of

Nutrients are believed to have a direct trophic effect on the cells of the gastrointestinal mucosa. However, no normal constituent of the diet has ever been shown to stimulate mucosal growth when administered orally. Sham-operated and antrectomized rats were fed 20 g of powdered commercial rat pellets daily or 20 g of food containing dimethylamine (100 mumol/g food). After 7 days rats were killed and growth of the mucosa of the oxyntic gland portion of the stomach and 2-cm segments of duodenum, jejunum, and proximal colon was determined. Antrectomy resulted in significant decreases in the weight and the DNA, RNA, and protein content of all four tissues and serum gastrin levels. Feeding amines abolished the differences in the oxyntic gland and duodenal mucosa. In general, the effect of amines decreased distally. Feeding amines did not significantly alter serum gastrin levels. These data indicate that dietary amines may directly stimulate the growth of gastrointestinal mucosa. These results may explain some of the proximal-to-distal gradients described for the growth of the mucosa.

Nonparallel secretion of enzymes by the rabbit pancreas

1986 ◽  
Vol 64 (3) ◽  
pp. 297-302 ◽  
Author(s):  
R. G. Lahaie ◽  
R. Michel ◽  
G. Michel ◽  
J. C. Dagorn
Keyword(s):  
Pancreatic Juice ◽  
Pancreatic Secretion ◽  
Exocrine Pancreas ◽  
Specific Activity ◽  
Experimental Models ◽  
Rabbit Pancreas ◽  
Protein Output ◽  
Recent Claim ◽  
Stimulation Of

Since nonparallel secretion of enzymes by the exocrine pancreas has been demonstrated with several experimental models, we were interested in verifying a recent claim that enzyme secretion remained strictly proportional (parallel) upon stimulation of the in vivo rabbit pancreas. Pancreatic juice was collected by extraduodenal cannulation of the pancreatic duct, in two different protocols. In the first protocol the administration of pentobarbital induces a mild anesthesia. Under this condition, amylase and chymotrypsin secretion remained parallel after cholecystokinin stimulation. In a second protocol, a deeper and constant anesthesia was attained with Fluothane resulting in a lower basal protein output than in the first protocol. Pancreatic secretion was collected under intravenous secretin perfusion (4.5 clinical units∙kg−1∙h−1). After stabilization and basal collection periods, pancreatic secretion was stimulated with an i.v. bolus injection of either cholecystokinin (2 Ivy dog units/kg), caerulein (0.1 μg/kg), or carbachol (6 μg/kg). Upon stimulation of the pancreas, protein output increased an average of 30-fold and there was a concomitant 20–25% decrease in the ratio of the specific activities of amylase to chymotrypsin which resulted from a greater increase in the specific activity of chymotrypsin in pancreatic juice after stimulation of secretion. Thus, under appropriate conditions, nonparallel secretion of enzymes by the exocrine pancreas can be demonstrated in yet another experimental model. Furthermore, the proportion of amylase and chymotrypsin activities in pancreatic juice are once more shown to be dependent, up to a threshold, upon the rate of protein output by this exocrine gland.

Cholecystokinin in the regulation of intestinal motility and pancreatic secretion in dogs

1988 ◽  
Vol 255 (4) ◽  
pp. G498-G504 ◽  
Author(s):  
P. Thor ◽  
J. Laskiewicz ◽  
P. Konturek ◽  
S. J. Konturek
Keyword(s):  
Small Bowel ◽  
Spike Activity ◽  
Pancreatic Secretion ◽  
Intestinal Motility ◽  
Motility Pattern ◽  
Motor Complex ◽  
Pancreatic Fistulas ◽  
Cck Antagonists ◽  
Cck Receptor Antagonists ◽  
Stimulation Of

Peptidal (CR-1409) and nonpeptidal (L-364,718) cholecystokinin (CCK) receptor antagonists were used to determine the possible involvement of CCK in the fasted and fed intestinal motility patterns and the related alterations in pancreatic secretion. Dogs were implanted with electrodes along the small bowel and with chronic pancreatic fistulas. In fasted dogs, the typical migrating motor complex (MMC) cycles and accompanying fluctuations in pancreatic secretion were recorded. Neither of the CCK antagonists affected these motor and secretory components of the MMC. Feeding interrupted the MMC and increased spike activity at all levels of the small bowel, and this was accompanied by a significant increase in pancreatic secretion and in plasma hormone [gastrin, CCK, and pancreatic polypeptide (PP)] levels. Both CCK antagonists significantly reduced the postprandial spike activity but failed to restore the fasted pattern. Exogenous gastrin and CCK, as well as bombesin, induced fedlike motility patterns accompanied by marked pancreatic protein secretion. These effects were completely reversed to the fasted patterns during intravenous infusion of CCK antagonists. In contrast, cholinergic stimulation (bethanechol) induced a fedlike pattern that was more resistant to CCK antagonists. We conclude that CCK does not play a major role in the fasted motility pattern and related fluctuations in pancreatic secretion but may be partly involved (by itself and by released PP) in the induction of the fed motility pattern and the postprandial stimulation of the exocrine pancreas.

scholarly journals Somatostatin levels and binding in duodenal mucosa of rabbits with ligation of the pancreatic duct

1988 ◽  
Vol 118 (2) ◽  
pp. 227-232 ◽  
Author(s):  
L. G. Guijarro ◽  
E. Arilla
Keyword(s):  
Pancreatic Duct ◽  
Binding Sites ◽  
Exocrine Pancreas ◽  
Duodenal Mucosa ◽  
Physiological Significance ◽  
Scatchard Analysis ◽  
Pancreatic Duct Ligation ◽  
Parallel Increase ◽  
Duct Ligation ◽  
Number Of Binding Sites

ABSTRACT Atrophy of the exocrine pancreas was induced in rabbits by pancreatic duct ligation. Somatostatin concentration and binding in cytosol from rabbit duodenal mucosa were studied after 6 and 14 weeks of pancreatic duct ligation. Somatostatin-like immunoreactivity was significantly increased in the duodenal mucosa in both periods. Scatchard analysis showed a parallel increase in the number of binding sites rather than a change in their affinity. The physiological significance of these findings remains to be clarified. J. Endocr. (1988) 118, 227–232

Microinjection of exogenous somatostatin in the dorsal vagal complex inhibits pancreatic secretion via somatostatin receptor-2 in rats

2007 ◽  
Vol 292 (3) ◽  
pp. G746-G752 ◽  
Author(s):  
Zhuan Liao ◽  
Zhao-Shen Li ◽  
Yan Lu ◽  
Wei-Zhong Wang
Keyword(s):  
Pancreatic Secretion ◽  
Exocrine Pancreas ◽  
Feedback Inhibition ◽  
Somatostatin Receptor ◽  
Inhibitory Effect ◽  
Receptor Subtype ◽  
Dependent Manner ◽  
Dorsal Vagal Complex ◽  
Somatostatin Receptor Antagonist ◽  
Dose Dependent

Previous studies have suggested that somatostatin inhibits pancreatic secretion at a central vagal site, and the dorsal vagal complex (DVC) is involved in central feedback inhibition of the exocrine pancreas. The aim of this study was to investigate the effect of exogenous somatostatin in the DVC on pancreatic secretion and the somatostatin receptor subtype(s) responsible for the effect. The effects of somatostatin microinjected into the DVC on pancreatic secretion stimulated by cholecystokinin octapeptide (CCK-8) or 2-deoxy-d-glucose (2-DG) were examined in anesthetized rats. To investigate the somatostatin inhibitory action site, a somatostatin receptor antagonist [SRA; cyclo(7-aminoheptanoyl-Phe-d-Trp-Lys-Thr)] was microinjected into the DVC before intravenous infusion of somatostatin and CCK-8/2-DG. The effects of injection of a somatostatin receptor-2 agonist (seglitide) and combined injection of somatostatin and a somatostatin receptor-2 antagonist (CYN 154806) in the DVC on the pancreatic secretion were also investigated. Somatostatin injected into the DVC significantly inhibited pancreatic secretion evoked by CCK-8 or 2-DG in a dose-dependent manner. SRA injected into the DVC completely reversed the inhibitory effect of intravenous administration of somatostatin. Seglitide injected into the DVC also inhibited CCK-8/2-DG-induced pancreatic protein secretion. However, combined injection of somatostatin and CYN 154806 did not affect the CCK-8/2-DG-induced pancreatic secretion. Somatostatin in the DVC inhibits pancreatic secretion via somatostatin receptor-2, and the DVC is the action site of somatostatin for its inhibitory effect.

scholarly journals Somatostatin and gastrointestinal tract. Clinical experiences

2013 ◽  
Vol 154 (39) ◽  
pp. 1535-1540 ◽  
Author(s):  
László Herszényi ◽  
Emese Mihály ◽  
Zsolt Tulassay
Keyword(s):  
Gastrointestinal Tract ◽  
Gastrointestinal Hormones ◽  
Gastrointestinal Diseases ◽  
Somatostatin Analogues ◽  
Therapeutic Modality ◽  
Exocrine Function ◽  
Somatostatin Analogue ◽  
Clinical Experiences ◽  
Pancreatic Fistulas ◽  
Long Acting

The effect of somatostatin on the gastrointestinal tract is complex; it inhibits the release of gastrointestinal hormones, the exocrine function of the stomach, pancreas and bile, decreases motility and influences absorption as well. Based on these diverse effects there was an increased expectation towards the success of somatostatin therapy in various gastrointestinal disorders. The preconditions for somatostatin treatment was created by the development of long acting somatostatin analogues (octreotide, lanreotide). During the last twenty-five years large trials clarified the role of somatostatin analogues in the treatment of various gastrointestinal diseases. This study summarizes shortly these results. Somatostatin analogue treatment could be effective in various pathological conditions of the gastrointestinal tract, however, this therapeutic modality became a part of the clinical routine only in neuroendocrine tumours and adjuvant treatment of oesophageal variceal bleeding and pancreatic fistulas. Orv. Hetil., 2013, 154, 1535–1540.

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