Pancreatic polypeptide inhibits pancreatic enzyme secretion via a cholinergic pathway

1987 ◽  
Vol 253 (5) ◽  
pp. G706-G710 ◽  
Author(s):  
G. Jung ◽  
D. S. Louie ◽  
C. Owyang
Keyword(s):  
Pancreatic Polypeptide ◽  
Acetylcholine Release ◽  
Pancreatic Enzyme ◽  
Enzyme Secretion ◽  
Dependent Manner ◽  
Amylase Release ◽  
Opioid Receptor Antagonists ◽  
Cholinergic Pathway ◽  
Pancreatic Enzyme Secretion ◽  
Dose Dependent

In rat pancreatic slices, rat pancreatic polypeptide (PP) or C-terminal hexapeptide of PP [PP-(31-36)] inhibited potassium-stimulated amylase release in a dose-dependent manner. The inhibition was unaffected by addition of hexamethonium but blocked by atropine. In contrast, PP(31-36) did not have any effect on acetylcholine- or cholecystokinin octapeptide-stimulated amylase release. In addition, when pancreatic slices were incubated with [3H] choline, PP(31-36) inhibited the potassium-evoked release of synthesized [3H] acetylcholine in a dose-dependent manner. The inhibitory action of PP was unaffected by adrenergic, dopaminergic, or opioid receptor antagonists. Thus PP inhibits pancreatic enzyme secretion via presynaptic modulation of acetylcholine release. This newly identified pathway provides a novel mechanism for hormonal inhibition of pancreatic enzyme secretion via modulation of the classic neurotransmitter function.

Cholecystokinin at physiological levels evokes pancreatic enzyme secretion via a cholinergic pathway

1992 ◽  
Vol 263 (1) ◽  
pp. G102-G107 ◽  
Author(s):  
H. C. Soudah ◽  
Y. Lu ◽  
W. L. Hasler ◽  
C. Owyang
Keyword(s):  
Acetylcholine Release ◽  
Pancreatic Enzyme ◽  
Exocrine Secretion ◽  
Cholinergic Innervation ◽  
Enzyme Secretion ◽  
Healthy Humans ◽  
Cholinergic Pathway ◽  
Pancreatic Enzyme Secretion ◽  
Stimulation Of

The mechanism by which physiological concentrations of cholecystokinin (CCK) evoke pancreatic exocrine secretion in humans was investigated. CCK octapeptide (CCK-8) dose dependently increased trypsin and lipase output in healthy humans. Atropine inhibited CCK-8 (10 ng.kg-1.h-1)-stimulated trypsin output by 84.0 +/- 7.7% and lipase output by 78.6 +/- 9.2%. The inhibition with atropine was much less with a CCK-8 dose of 40 ng.kg-1.h-1 (41.8 +/- 6.6% for trypsin and 46.3 +/- 7.3% for lipase). CCK-8 at 10 ng.kg-1.h-1 produced plasma CCK levels similar to postprandial levels (6.0 +/- 1.3 vs. 6.9 +/- 0.8 pM), whereas the 40-ng.kg-1.h-1 dose produced supraphysiological levels (18.4 +/- 3.1 pM). To evaluate if CCK might act via stimulation of cholinergic nerves, in vitro studies were performed using rat pancreas. CCK-8 (10 nM-10 microM) stimulated [3H]acetylcholine release from pancreatic lobules that was blocked by tetrodotoxin, a calcium-free medium, and the CCK antagonist L364,718. In conclusion, CCK-stimulated pancreatic enzyme secretion is dependent on cholinergic neural and noncholinergic pathways. In humans, CCK infusions, which produce plasma CCK levels similar to those seen postprandially, stimulate the pancreas predominantly via a pathway dependent on cholinergic innervation. Correlative in vitro experiments suggest that CCK may act by stimulation of neural acetylcholine release. In contrast, supraphysiological CCK infusions act in part via noncholinergic pathways.

Pancreastatin inhibits pancreatic enzyme secretion by presynaptic modulation of acetylcholine release

1992 ◽  
Vol 262 (1) ◽  
pp. G113-G117 ◽  
Author(s):  
K. H. Herzig ◽  
D. S. Louie ◽  
K. Tatemoto ◽  
O. Y. Chung
Keyword(s):  
Acetylcholine Release ◽  
Pancreatic Enzyme ◽  
Exocrine Secretion ◽  
Enzyme Secretion ◽  
Neural Pathways ◽  
Amylase Release ◽  
Pancreatic Acini ◽  
Presynaptic Modulation ◽  
Pancreatic Enzyme Secretion ◽  
Pancreatic Fistulas

Pancreastatin (PST), a 49-amino acid polypeptide, inhibits endocrine and exocrine pancreatic functions. In this study, we examined the mechanism of the inhibitory action of PST on exocrine pancreatic secretion in the rat. In anesthetized rats prepared with pancreatic fistulas, intravenous administration of PST (500 pM.kg-1.h-1) completely inhibited 2-deoxyglucose (75 mg/kg)-stimulated amylase output to below basal levels. Because 2-deoxyglucose acts to stimulate the vagus, we assessed the ability of PST to inhibit carbachol-stimulated amylase release from isolated rat pancreatic acini. PST suppressed neither carbachol- nor cholecystokinin-stimulated amylase release, indicating that PST inhibits exocrine secretion via indirect mechanisms. To examine neural pathways for inhibition, we used pancreatic lobules to examine the action of PST on intrapancreatic neurons. Incubation of pancreatic lobules in 75 mM potassium buffer stimulated amylase release by a cholinergic pathway. PST dose dependently inhibited potassium-evoked amylase release, with maximal inhibition of 49.6 +/- 11%. In addition, when lobules were incubated with [3H]choline, PST inhibited KCl-stimulated release of synthesized [3H]acetylcholine by 43 +/- 5.7%. Other studies demonstrate that PST inhibits rat pancreatic enzyme secretion via presynaptic modulation of acetylcholine release.

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 is not a peripheral satiety signal in the dog

1985 ◽  
Vol 249 (6) ◽  
pp. G733-G738
Author(s):  
T. N. Pappas ◽  
R. L. Melendez ◽  
K. M. Strah ◽  
H. T. Debas
Keyword(s):  
Pancreatic Enzyme ◽  
Cerebral Ventricle ◽  
Gastric Distension ◽  
Dependent Manner ◽  
Gallbladder Contraction ◽  
Sham Feeding ◽  
Pancreatic Enzyme Secretion ◽  
Pancreatic Fistulas ◽  
Dose Dependent ◽  
Lateral Cerebral Ventricle

The doses of cholecystokinin (CCK) that have been shown to cause satiety after peripheral administration are pharmacological and whether "physiological" doses of exogenous CCK or endogenously released CCK have a satiety effect is not known. The purpose of the present study is threefold: to compare the potency of endogenous and exogenous CCK for their satiety, cholecystokinetic, and pancreozyminic actions; to determine whether small doses of CCK in the presence of gastric distension cause satiety; and to test the satiety effect of CCK administered centrally into the lateral cerebral ventricle. Dogs were prepared with cerebroventricular guides and esophageal and duodenal fistulas (n = 4), with chronic bile fistulas (n = 8), and chronic pancreatic fistulas (n = 7). Satiety effect was quantified in the esophageal fistula dog by the amount of blenderized food sham fed within 7.5 min. Duodenal perfusion of fat, used as a releaser of endogenous CCK, stimulated pancreatic protein, and gallbladder contraction with D50 values of 1.5 and 0.3 mmol/h, respectively, but had no effect on the volume sham fed (316 +/- 82 ml/min without and 371 +/- 41 ml/min with the maximal dose of sodium oleate infused). The D50 values of CCK-8 (pmol X kg-1 X h-1) for satiety and for stimulation of pancreatic enzyme secretion and gallbladder contraction were 440, 120, and 22, respectively. Injection of CCK-8 into the lateral cerebral ventricle inhibited sham feeding in a dose-dependent manner. We conclude that duodenal fat in doses producing maximal gallbladder and pancreatic stimulation has no satiety effect in the dog.(ABSTRACT TRUNCATED AT 250 WORDS)

CK-independent increases in pancreatic secretion induced by dietary protein in chronic BPJ-diverted rats

1996 ◽  
Vol 271 (3) ◽  
pp. G501-G508
Author(s):  
H. Hara ◽  
T. Nishi ◽  
H. Narakino ◽  
T. Kasai
Keyword(s):  
Dietary Protein ◽  
Pancreatic Secretion ◽  
Pancreatic Enzyme ◽  
Oral Feeding ◽  
Enzyme Secretion ◽  
Cholinergic Pathway ◽  
Protein Ingestion ◽  
Pancreatic Enzyme Secretion ◽  
Cck Antagonist ◽  
Very High

Previously, we demonstrated that, in rats with chronic bile-pancreatic juice (BPJ) diversion, pancreatic enzyme secretion was increased after feeding animals a 25% casein fat-free diet. We determined whether cholecystokinin (CCK) or the cholinergic pathway is associated with the response of pancreatic secretion after protein ingestion in the diverted rats, using a potent CCK antagonist, MK-329 or FK-480, and a cholinergic blocker, atropine. Secretion rates of chymotrypsin and trypsin in the fasting state were very high 7 days after a BPJ diversion, and the hypersecretion of the proteases was markedly reduced with an injection of MK-329, FK-480, or atropine and was further reduced by combined injection of FK-480 and atropine. The lowered secretion of the proteases in CCK-antagonized rats was increased after oral feeding of a protein diet and after a duodenal instillation of some protein sources, especially hydrolysate of guanidinated casein (HGC). The CCK-independent increases by HGC instillation are completely depressed by atropine. In rats treated with only atropine, the lowered secretion tended to be increased by a duodenal instillation of HGC. Increases in secretion after an administration of the protein source in CCK-antagonized rats were not affected by bestatin, an inhibitor of brush-border peptidases. We conclude that the stimulatory effects of dietary protein on the pancreatic enzyme secretion partially do not depend on CCK in chronic BPJ-diverted rats and that the CCK-independent increase is atropine sensitive.

Action of pancreatic polypeptide on rat pancreatic secretion: in vivo and in vitro

1985 ◽  
Vol 249 (4) ◽  
pp. G489-G495 ◽  
Author(s):  
D. S. Louie ◽  
J. A. Williams ◽  
C. Owyang
Keyword(s):  
Protein Secretion ◽  
Pancreatic Polypeptide ◽  
Pancreatic Secretion ◽  
Specific Binding ◽  
Pancreatic Enzyme ◽  
Enzyme Secretion ◽  
Amylase Release ◽  
Pancreatic Acini

The biological activity of bovine pancreatic polypeptide (BPP) on rat exocrine pancreatic secretion was compared in vivo and in vitro. In anesthetized rats prepared with a bile-pancreatic duct cannula, BPP inhibited cholecystokinin (CCK)-stimulated (10 IDU . kg-1 X h-1) protein secretion in a dose-related manner (P less than 0.001). CCK, from 5-20 IDU . kg-1 X h-1, did not alter the degree of inhibition by BPP at 40 micrograms . kg-1 X h-1, suggesting a nonsurmountable inhibition. Analogues of BPP, including rat pancreatic polypeptide, neuropeptide Y, peptide YY, and the C-terminal hexapeptide of PP, also inhibited CCK-stimulated protein secretion. To determine whether BPP acts directly on acinar cells to suppress enzyme secretion, in vitro studies were performed. BPP and its analogues did not suppress octapeptide of CCK (CCK-8)-stimulated amylase release from either isolated rat pancreatic acini or preparations of pancreatic lobules. Specific binding of 125I-BPP to pancreatic acini was also not observed. From our data we conclude that BPP acts to inhibit pancreatic enzyme secretion in the rat in a noncompetitive manner. Absence of an effect by BPP or its analogues in vitro coupled with an absence of 125I-BPP binding to acini suggest that the inhibitory action of PP on exocrine pancreatic function is mediated by indirect mechanisms.

Efficacy of octreotide (Octrade) for prevention of pancreatitis after endoscopic retrograde cholangiopancreatography

2020 ◽  
Vol 1 (30) ◽  
pp. 30-36
Author(s):  
E. A. Krylova ◽  
D. V. Aleinik
Keyword(s):  
Endoscopic Retrograde Cholangiopancreatography ◽  
Intravenous Infusion ◽  
Pancreatic Enzyme ◽  
Enzyme Secretion ◽  
Continuous Intravenous Infusion ◽  
Endoscopic Retrograde ◽  
Pancreatic Enzyme Secretion

The article presents the results of a study of the effectiveness of the use of an inhibitor of pancreatic enzyme secretion of octreotide (Octrade) for the prevention of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). It was shown that the administration of Octrade at a dose of 0.3 mg in 500 ml of 0.9 % NaCl by continuous intravenous infusion for 7 hours and then 0.1 mg of Octrade subcutaneously at 6 and 12 hours after the end of intravenous infusion significantly reduced the frequency of pancreatitis (4.0 % and 22.2 %; p < 0.05) and hyperamylasemia (8.0 % and 25.9 %; p < 0.05) after ERCP. It is concluded that Octrade is effective in preventing the development of pancreatitis and hyperamilasemia after ERCP.

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