Somatostatin inhibits CCK release by inhibiting secretion and action of CCK-releasing peptide

1994 ◽  
Vol 266 (6) ◽  
pp. G1156-G1161
Author(s):  
K. H. Herzig ◽  
D. S. Louie ◽  
C. Owyang
Keyword(s):  
Pancreatic Juice ◽  
Inhibitory Action ◽  
Pancreatic Enzyme ◽  
Feedback Regulation ◽  
Amylase Secretion ◽  
Amylase Output ◽  
Pancreatic Enzyme Secretion ◽  
Mucosal Explants ◽  
Intraduodenal Administration ◽  
Cck Release

We hypothesized that somatostatin exerts its inhibitory action on cholecystokinin (CCK) release and pancreatic secretion by inhibiting the secretion and/or action of a CCK-releasing peptide (CCK-RP) secreted from the small intestine. Our studies demonstrated that intravenous infusion of somatostatin (25 micrograms.kg-1.h-1) completely inhibited the increase in amylase output evoked by diversion of bile-pancreatic juice and 80 +/- 10% of the increase in plasma CCK. Intraduodenal administration of concentrated intestinal perfusate containing the CCK-RP collected from a donor rat with bile-pancreatic juice diversion raised amylase output by 2.3-fold and elevated plasma CCK levels to 7 +/- 0.8 pM in a recipient rat. The stimulatory effect of the concentrated intestinal washings was abolished when the "donor" rat was pretreated with somatostatin. In addition, in somatostatin-treated "recipient" rats, intraduodenal administration of intestinal washings containing CCK-RP also failed to elicit an increase in plasma CCK and amylase secretion. Furthermore, using duodenal mucosal explants, we demonstrated that the inhibitory action of somatostatin on CCK release evoked by CCK-RP was antagonized by pretreatment with pertussis toxin. These observations strongly suggest that somatostatin inhibits feedback regulation of pancreatic enzyme secretion by inhibiting both the secretion and action of CCK-RP.

A cholecystokinin releasing peptide mediates feedback regulation of pancreatic secretion

1989 ◽  
Vol 256 (2) ◽  
pp. G430-G435 ◽  
Author(s):  
L. Lu ◽  
D. Louie ◽  
C. Owyang
Keyword(s):  
Pancreatic Juice ◽  
Pancreatic Enzyme ◽  
Feedback Regulation ◽  
Enzyme Secretion ◽  
Amylase Output ◽  
Stimulatory Activity ◽  
Pancreatic Enzyme Secretion ◽  
Rapid Perfusion ◽  
Intestinal Fistulas ◽  
Cck Release

Diversion of bile pancreatic juice from the duodenum in rats stimulates cholecystokinin (CCK) release and pancreatic enzyme secretion. Intraduodenal perfusion of trypsin inhibits the release of CCK and pancreatic enzyme secretion. We hypothesized that the increased pancreatic enzyme secretion after pancreatic juice diversion is mediated by a trypsin-sensitive peptide secreted by the small intestine that stimulates release of CCK. To test this hypothesis, rats were surgically prepared with bile-pancreatic cannula and intestinal fistulas. Diversion of bile-pancreatic juice stimulated amylase output fivefold above basal and increased plasma CCK from a basal of 0.5 +/- 0.05 pM to 14 +/- 5 pM. Rapid perfusion (3 ml/min) of the duodenum with phosphate-buffered saline reversed the increase in amylase output and lowered the plasma CCK to 1.2 +/- 0.2. Administration of intestinal perfusate (3 ml/min) collected from a donor rat into the duodenum of a recipient rat with diversion of bile pancreatic juice increased amylase output threefold above basal and increased plasma CCK. The stimulatory activity of the intestinal perfusate was inactivated by treatment with trypsin but not by amylase or lipase. In addition, boiling did not alter the stimulatory activity of the intestinal perfusate. Perfusion of intestinal perfusate from donor rats pretreated with atropine did not stimulate amylase output and CCK release in recipient rats. By use of molecular membrane exclusion filters, stimulatory activity was retained (between 1,000 and 5,000). These results indicate that feedback regulation of pancreatic enzyme secretion is mediated by a CCK releasing peptide whose secretion from the duodenum is cholinergically mediated. This peptide is trypsin sensitive and has a molecular weight between 1,000 and 5,000.

Effect of CCK antagonist L 364718 on meal-induced pancreatic secretion in rats

1990 ◽  
Vol 258 (2) ◽  
pp. G179-G184 ◽  
Author(s):  
M. F. O'Rourke ◽  
R. D. Reidelberger ◽  
T. E. Solomon
Keyword(s):  
Pancreatic Secretion ◽  
Competitive Inhibition ◽  
Pancreatic Enzyme ◽  
Enzyme Secretion ◽  
Amylase Secretion ◽  
Liquid Meal ◽  
Amylase Output ◽  
Pancreatic Enzyme Secretion ◽  
Cck Receptor Antagonist

The specific cholecystokinin (CCK)-receptor antagonist L 364718 was used to examine the role of CCK in meal-induced pancreatic secretion. Unanesthetized rats with gastric, jugular vein, bilepancreatic, and duodenal cannulas were used; bile-pancreatic juice was recirculated. Basal amylase secretion (30% of maximal) was not inhibited by L 364718 doses of 0.5 or 2 mg/kg intravenously. L 364718 (0.02 to 2 mg/kg) caused dose-related inhibition of the maximal amylase response to CCK-8 (200 pmol.kg-1.h-1), with greater than 80% inhibition at doses greater than or equal to 0.5 mg/kg. L 364718 (0.5 mg/kg) shifted the dose-response curve to CCK-8 (25-3,200 pmol.kg-1.h-1) to the right (ED50 increased 10-fold) but did not alter maximal amylase output consistent with competitive inhibition of CCK in vivo. Ingestion of liquid food significantly increased amylase output threefold above basal. L 364718 (0.5 mg/kg) completely blocked this response. These results suggest that although CCK does not regulate basal pancreatic enzyme secretion, it is the primary mediator of pancreatic enzyme secretion in response to a liquid meal.

Stimulus–secretion coupling in exocrine pancreas: possible role of calmodulin

1981 ◽  
Vol 59 (9) ◽  
pp. 994-1001 ◽  
Author(s):  
Seymour Heisler ◽  
Laurence Chauvelot ◽  
Diane Desjardins ◽  
Christiane Noel ◽  
Herman Lambert ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Pancreatic Enzyme ◽  
Antidepressant Drugs ◽  
Enzyme Secretion ◽  
Pancreatic Acinar Cells ◽  
Secretory Process ◽  
Amylase Secretion ◽  
Enzyme Release ◽  
Mediated Effects ◽  
Pancreatic Enzyme Secretion

Many calcium-mediated effects in mammalian cells may be activated by calcium-calmodulin stimulated enzymes. These effects are inhibited by various antidepressant drugs which bind to and inactivate calmodulin. In the current study, calmodulin was identified by affinity chromatography and gel electrophoresis in the cytoplasm of dispersed rat pancreatic acinar cells. Its role in enzyme secretion was assessed by evaluating the effects of various antidepressant drugs on the enzyme secretory process. Chlorpromazine, trifluoperazine, thioridazine, chlorprothixene and amitriptyline inhibited amylase secretion stimulated by carbacol, A-23187, and cholecystokinin-pancreozymin but not that elicitied by dibutyryl cyclic AMP secretin or vasoactive intestinal peptide (VIP). Haloperidol, sulpiride, phenobarbital, and ethanol were without effect on secretagogue-stimulated enzyme release. Only those agents which blocked secretion also inhibited 45Ca release stimulated by carbachol from isotope preloaded cells. The data suggest that calmodulin may have a functional role in pancreatic enzyme secretion.

Bovine pancreatic polypeptide as an antagonist of muscarinic cholinergic receptors

1987 ◽  
Vol 252 (3) ◽  
pp. G384-G391
Author(s):  
G. Z. Pan ◽  
L. Lu ◽  
J. M. Qian ◽  
B. G. Xue
Keyword(s):  
Pancreatic Polypeptide ◽  
Pancreatic Enzyme ◽  
Cholinergic Receptors ◽  
Enzyme Secretion ◽  
Amylase Secretion ◽  
Enzyme Release ◽  
Muscarinic Cholinergic Receptors ◽  
Bovine Pancreatic Polypeptide ◽  
Pancreatic Enzyme Secretion ◽  
Muscarinic Cholinergic

In dispersed acini from rat pancreas, it was found that bovine pancreatic polypeptide (BPP) and its C-fragment hexapeptide amide (PP-6), at concentrations of 0.1 and 30 microM, respectively, could significantly inhibit amylase secretion stimulated by carbachol (P less than 0.01 or 0.05, respectively), and this inhibition by BPP was dose dependent. 45Ca outflux induced by carbachol was also inhibited by BPP or PP-6, but they had no effect on cholecystokinin octapeptide- (CCK-8) or A23187-stimulated 45Ca outflux. BPP was also capable of displacing the specific binding of [3H]quinuclidinyl benzilate to its receptors, and it possessed a higher affinity (ki 35 nM) than carbachol (Ki 1.8 microM) in binding with M-receptors. It is concluded from this study that BPP acts as an antagonist of muscarinic cholinergic receptors in rat pancreatic acini. In addition, BPP inhibited the potentiation of amylase secretion caused by the combination of carbachol plus secretin or vasoactive intestinal peptide. This may be a possible explanation of the inhibitory effect of BPP on secretin-induced pancreatic enzyme secretion shown in vivo, since pancreatic enzyme secretion stimulated by secretin under experimental conditions may be the result of potentiation of enzyme release produced by the peptide in combination with a cholinergic stimulant.

Cholecystokinin suppresses food intake by a nonendocrine mechanism in rats

1994 ◽  
Vol 267 (4) ◽  
pp. R901-R908 ◽  
Author(s):  
R. D. Reidelberger ◽  
G. Varga ◽  
R. M. Liehr ◽  
D. A. Castellanos ◽  
G. L. Rosenquist ◽  
...  
Keyword(s):  
Food Intake ◽  
Pancreatic Enzyme ◽  
Free Access ◽  
Amylase Secretion ◽  
Receptor Antagonists ◽  
Feeding Experiments ◽  
Pancreatic Enzyme Secretion ◽  
Endocrine Mechanism ◽  
Access To Food ◽  
Cck Receptor Antagonists

A cholecystokinin monoclonal antibody (CCK MAb) was used to immunoneutralize CCK to test the hypothesis that CCK produces satiety by an endocrine mechanism. We first characterized the effects of CCK MAb on pancreatic secretion. Conscious rats with jugular vein and bile-pancreatic duct cannulas received CCK MAb or control antibody intravenously 30 min before a 2-h maximal dose of CCK-8 (200 pmol.kg-1.h-1 i.v.) or access to food. CCK MAb caused dose-related inhibition of amylase secretion. CCK MAb (2 mg/kg) completely blocked the response to CCK-8 and inhibited the response to food by 89%. In feeding experiments, rats with free access to food received CCK MAb or control antibodies (2 mg/kg iv) 2 h after lights off. CCK MAb had no effect on 1.5- or 3.5-h food intake. Another group of rats received CCK MAb (4 mg/kg i.v.) or a combined injection of type A and type B CCK receptor antagonists devazepide and L-365,260 (1 mg/kg each i.v.). CCK MAb had no effect on feeding, whereas the receptor antagonists stimulated 1-, 2-, 3-, and 4-h intake by 62, 45, 43, and 29%. These results suggest that endogenous CCK stimulates pancreatic enzyme secretion at least partially by an endocrine mechanism and produces satiety by a nonendocrine mechanism.

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