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.

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.

Evidence for an Intraluminal Mediator in Rat Pancreatic Enzyme Secretion: Reconstitution of the Pancreatic Response with Dietary Protein, Trypsin and the Monitor Peptide

1989 ◽  
Vol 119 (4) ◽  
pp. 622-627 ◽  
Author(s):  
Tohru Fushiki ◽  
Hideaki Kajkira ◽  
Shin-Ichi Fukuoka ◽  
Keishi Kido ◽  
Toshihiko Semba ◽  
...  
Keyword(s):  
Dietary Protein ◽  
Pancreatic Enzyme ◽  
Enzyme Secretion ◽  
Pancreatic Enzyme Secretion

Somatostatin inhibits pancreatic enzyme secretion at a central vagal site

1993 ◽  
Vol 265 (2) ◽  
pp. G251-G257 ◽  
Author(s):  
Y. Li ◽  
C. Owyang
Keyword(s):  
Effective Dose ◽  
Protein Secretion ◽  
Pancreatic Secretion ◽  
Inhibitory Action ◽  
Pancreatic Enzyme ◽  
Enzyme Secretion ◽  
Afferent Pathway ◽  
Pancreatic Enzyme Secretion ◽  
Vagal Afferent ◽  
Somatostatin 14

The mechanisms and site of action of somatostatin-induced inhibition of pancreatic enzyme secretion were investigated using different stimulants of pancreatic secretion acting on different sites in anesthetized rats. Administration of graded doses of somatostatin-14 resulted in a dose-related inhibition of pancreatic protein secretion evoked by 2-deoxy-D-glucose, a central vagal stimulant that acts by stimulating the dorsal vagal nuclei. The lowest effective dose of somatostatin-14 was 1.0 microgram.kg-1 x h-1; maximal effective dose was 25 micrograms.kg-1 x h-1, which resulted in complete inhibition of protein output. Similarly, somatostatin-14 at a dose of 25 micrograms.kg-1 x h-1 also completely inhibited pancreatic protein secretion in response to a physiological concentration of cholecystokinin octapeptide (CCK-8), which acts via a vagal afferent pathway. In contrast, pancreatic protein outputs evoked by bethanechol, which directly stimulates pancreatic muscarinic receptors, or electrical stimulation of the vagal trunk, which activates the vagal efferent pathway, were unaffected by somatostatin-14. In separate studies, we demonstrated that perivagal treatment with the sensory neurotoxin capsaicin impaired pancreatic responses to CCK-8 but had no effect on the inhibitory action of somatostatin-14 on pancreatic secretion evoked by 2-deoxy-D-glucose, ruling out an effect of somatostatin on the vagal afferent pathway. Similarly we also demonstrated that perineural capsaicin treatment of the celiac-superior mesenteric ganglia did not affect the inhibitory action of somatostatin. These findings indicate that somatostatin inhibits 2-deoxy-D-glucose- and CCK-8-evoked pancreatic enzyme secretion via a vagal pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Physiological mechanisms of cholecystokinin action on pancreatic secretion

1996 ◽  
Vol 271 (1) ◽  
pp. G1-G7 ◽  
Author(s):  
C. Owyang
Keyword(s):  
Pancreatic Secretion ◽  
Pancreatic Enzyme ◽  
Experimental Studies ◽  
Sensory Information ◽  
Pancreatic Acini ◽  
Gastroduodenal Mucosa ◽  
Wide Range ◽  
Cholinergic Pathway ◽  
Pancreatic Enzyme Secretion ◽  
The Central Nervous System

Recent experimental studies in animals and humans provide strong evidence that cholecystokinin (CCK) acts via cholinergic pathways to mediate pancreatic enzyme secretion. These studies indicate that the sites of CCK's action to stimulate pancreatic secretion are dose dependent. Doses of CCK that produce physiological plasma CCK levels act via stimulation of the vagal afferent pathway originating from the gastroduodenal mucosa, whereas doses that produce supraphysiological CCK levels act to stimulate intrapancreatic neurons and pancreatic acini. These CCK-sensitive fibers are also responsive to a wide range of chemical and osmotic stimuli. In this manner, gastrointestinal afferents responding to hormones such as CCK and the ever-changing chemical and physical luminal environment provide sensory information to the central nervous system, which in turn stimulates pancreatic secretion via a vagal cholinergic pathway.

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.

Central CGRP inhibits pancreatic enzyme secretion by modulation of vagal parasympathetic outflow

1998 ◽  
Vol 275 (5) ◽  
pp. G957-G963 ◽  
Author(s):  
Ying Li ◽  
Yi Cheng Jiang ◽  
Chung Owyang
Keyword(s):  
Nervous System ◽  
Protein Secretion ◽  
Pancreatic Secretion ◽  
Inhibitory Action ◽  
Pancreatic Enzyme ◽  
Enzyme Secretion ◽  
Intravenous Route ◽  
Neural Pathways ◽  
Vagus Nerves ◽  
Pancreatic Enzyme Secretion

Calcitonin gene-related peptide (CGRP) is a potent inhibitor of pancreatic enzyme secretion in vivo. Recent studies have shown that CGRP exerts its inhibitory action at a central vagal site. The present study investigates the mechanism responsible for the central action of CGRP. Rats were fitted with lateral cerebroventricular cannulas, using stereotaxic instruments, 4 days before pancreatic secretion studies. In anesthetized rats, administration of 2-deoxy-d-glucose (2-DG) (75 mg/kg iv) or CCK-8 (40 pmol ⋅ kg−1 ⋅ h−1) produced a 100 and 75% increase in protein secretion, respectively, which was completely blocked by atropine. Intracerebroventricular (ICV) administration of CGRP (0.03–0.6 nmol/h) resulted in a dose-related inhibition of pancreatic protein secretion evoked by 2-DG or CCK-8. CGRP administered by the ICV route was 10–40 times more potent than CGRP given by the intravenous route. In contrast, ICV administration of CGRP had no significant effect on pancreatic protein secretion evoked by electrical vagal stimulation or bethanechol, which directly activates the pancreatic muscarinic receptor. Chemical sympathectomy induced by pretreatment with guanethedine (20 mg/kg ip, 2 days) or α-adrenergic receptor blockade with phentolamine did not alter the inhibitory effects of CGRP. We recently demonstrated that CCK stimulated the enteropancreatic neural pathways to mediate pancreatic secretion in rats with a chronic vagotomy. ICV-administered CGRP did not affect CCK-stimulated pancreatic secretion in rats with a chronic vagotomy. In conclusion, CGRP in the central nervous system inhibits pancreatic enzyme secretion stimulated by 2-DG and CCK-8, which act through vagal pathways. The inhibitory action of CGRP is not mediated by the sympathetic nervous system but appears to depend on intact vagus nerves.

Cholecystokinin mediates feedback regulation of pancreatic enzyme secretion in rats

1986 ◽  
Vol 250 (2) ◽  
pp. G252-G259 ◽  
Author(s):  
D. S. Louie ◽  
D. May ◽  
P. Miller ◽  
C. Owyang
Keyword(s):  
Negative Feedback ◽  
Intravenous Infusion ◽  
Pancreatic Secretion ◽  
Pancreatic Enzyme ◽  
Feedback Regulation ◽  
Enzyme Secretion ◽  
Negative Feedback Regulation ◽  
Plasma Cholecystokinin ◽  
Pancreatic Enzyme Secretion ◽  
Protein Output

Previous studies have shown that trypsin and chymotrypsin in the duodenum exert a negative-feedback regulation on pancreatic enzyme secretion in the rat. The mechanism responsible for this physiological phenomenon is unknown. By use of a specific and sensitive bioassay based on amylase release from isolated pancreatic acini, the role of cholecystokinin in the negative-feedback regulation of exocrine pancreatic secretion was examined. Rats were prepared with duodenal cannulas and pancreaticobiliary cannulas. Diversion of pancreaticobiliary juice resulted in a threefold increase in pancreatic protein output and an increase of plasma cholecystokinin from a basal level of 0.5 +/- 0.08 pM cholecystokinin octapeptide (CCK-8) to 16 +/- 4 pM CCK-8. Perfusion of trypsin (2 mg/h) or pancreaticobiliary juice returned pancreatic protein output to basal levels and plasma cholecystokinin to 2.1 +/- 1.2 and 0.33 +/- 0.1 pM, respectively. The inhibitory effect of trypsin on cholecystokinin release was enzyme and site specific, since inhibition of cholecystokinin release was not observed with perfusion of amylase into the duodenum or with trypsin into the ileum. Intravenous infusion of proglumide abolished the increase in pancreatic secretion following diversion of pancreaticobiliary juice. Intraduodenal perfusion of lidocaine, infusion of tetrodotoxin into the superior mesenteric artery, or intravenous infusion of atropine inhibited the rise in plasma cholecystokinin seen with diversion of pancreaticobiliary juice. These studies suggest that feedback regulation of pancreatic enzyme secretion in the rat is mediated by release of cholecystokinin. Furthermore, the feedback mechanism is neurally mediated, involving a cholinergic pathway.

Human pancreatic secretion and intestinal motility: effects of ileal nutrient perfusion

1990 ◽  
Vol 258 (2) ◽  
pp. G196-G201 ◽  
Author(s):  
P. Layer ◽  
S. Peschel ◽  
T. Schlesinger ◽  
H. Goebell
Keyword(s):  
Pancreatic Secretion ◽  
Intestinal Motility ◽  
Healthy Subjects ◽  
Pancreatic Enzyme ◽  
Essential Amino Acids ◽  
Enzyme Secretion ◽  
Duodenal Juice ◽  
Distal Small Intestine ◽  
Pancreatic Enzyme Secretion ◽  
Stimulation Of

To study the effects of intraileal nutrients on human pancreatic secretion and gastrointestinal motility, nine healthy subjects were intubated with an oroileal multilumen tube for ileal perfusion, duodenal juice aspiration, and intestinal motility recording. The duodenum was perfused continuously with essential amino acids to induce submaximal stimulation of pancreatic enzyme secretion and fed motility pattern. Additional ileal perfusion with carbohydrate at quantities similar to those observed under physiological late postprandial conditions or fat at isocaloric loads significantly decreased pancreatic enzyme outputs by greater than 80% (P less than 0.001) compared with saline. Ileal carbohydrate or fat induced a duodenal motor activity front that migrated distally and was followed by reduced motility. In summary, ileal delivery of small quantities of nutrient markedly decreased endogenously stimulated pancreatic enzyme secretion in humans. This was associated with specific changes in fed intestinal motility that converted to patterns characteristic of the interdigestive state. Our findings suggest that the distal small intestine may participate in the late postprandial regulation of gastrointestinal function in humans.

Sign in / Sign up

Export Citation Format

Share Document