Water and enzyme secretion are tightly coupled in pancreatic secretion stimulated by food or CCK-58 but not by CCK-8

Pancreatic secretion of protein, water, chloride, and bicarbonate under basal conditions and in response to intravenous and intraduodenal stimuli were studied in awake rats fully recovered from surgery. During the basal phase of pancreatic secretion, protein output and water output were weakly correlated or uncorrelated, consistent with separate regulation and distinct cellular origin of enzyme (acinar cells) and water (duct cells), referred to as the two-component paradigm of pancreatic secretion. When pancreatic secretion was stimulated physiologically, water and protein output abruptly became strongly and significantly correlated, suggesting that protein secretion and water secretion are tightly coupled or that protein secretion is dependent on water secretion. The apparent function of this coupling is to resist or prevent increases in protein concentration as protein output increases. This pattern of secretion was reproduced by intravenous infusion of the CCK-58 form of cholecystokinin, which strongly stimulates pancreatic water and chloride secretion, but not by CCK-8, which only weakly stimulates water and chloride secretion in a non-dose-dependent manner. The remarkably tight association of water and protein secretion in food-stimulated and CCK-58-stimulated pancreatic secretion is consistent with a single cell type as the origin of both water and enzyme secretion, i.e., the acinar cell, and is not consistent with the two-component paradigm of pancreatic secretion. Because CCK-58 is the only detectable endocrine form of cholecystokinin in the rat and its bioactivity pattern is markedly and qualitatively different from CCK-8, actions previously recorded for CCK-8 should be reexamined.

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Somatostatin inhibits pancreatic enzyme secretion at a central vagal site

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1993.265.2.g251 ◽

1993 ◽

Vol 265 (2) ◽

pp. G251-G257 ◽

Cited By ~ 4

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)

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

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1985.249.4.g489 ◽

1985 ◽

Vol 249 (4) ◽

pp. G489-G495 ◽

Cited By ~ 9

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.

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Plasma secretin, CCK, and pancreatic secretion in response to dietary fat in the rat

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1989.256.6.g1016 ◽

1989 ◽

Vol 256 (6) ◽

pp. G1016-G1021 ◽

Cited By ~ 9

Author(s):

G. M. Green ◽

S. Taguchi ◽

J. Friestman ◽

W. Y. Chey ◽

R. A. Liddle

Keyword(s):

Protein Secretion ◽

Trypsin Inhibitor ◽

Dietary Fat ◽

Pancreatic Secretion ◽

Intraduodenal Infusion ◽

Reduced Fat ◽

Plasma Cholecystokinin ◽

Protein Output ◽

Secretin Release

The role of fat in regulation of pancreatic secretion was studied in conscious rats by measuring pancreatic secretion and plasma cholecystokinin (CCK) and secretin responses to intraluminal infusion of fat, protein, or trypsin inhibitor via the duodenum. In rats with pancreatic juice continuously returned to the intestine, intraduodenal infusion of 20% emulsified fat (Liposyn), 10% casein, and 0.4% ovomucoid trypsin inhibitor (OMTI) stimulated equivalent increases of approximately threefold in pancreatic protein output. Proglumide reduced fat-stimulated pancreatic protein secretion by greater than 90% but did not inhibit the response to OMTI. Fat significantly increased plasma CCK from basal levels of 0.5 pM to 2-3 pM, but it was a weaker stimulant of CCK secretion than casein (peak CCK levels greater than 10 pM) or OMTI (peak CCK levels 5-6 pM). Fat significantly stimulated secretin release (21.7 pM) compared with casein (6.8 pM), OMTI (4.4 pM), and NaCl (3.5 pM). The inhibition of fat-stimulated pancreatic secretion by proglumide indicates that the small amounts of CCK released by fat are necessary for a normal pancreatic response, suggesting that this response may be the result of potentiation between secretin and small amounts of CCK.

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Neurohormonal mechanism of pancreatic exocrine secretion stimulated by sodium oleate and L-tryptophan in dogs

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1992.263.1.g12 ◽

1992 ◽

Vol 263 (1) ◽

pp. G12-G16 ◽

Cited By ~ 1

Author(s):

Y. H. Jo ◽

Y. L. Lee ◽

K. Y. Lee ◽

T. M. Chang ◽

W. Y. Chey

Keyword(s):

Pancreatic Juice ◽

Sodium Oleate ◽

Pancreatic Secretion ◽

Exocrine Secretion ◽

Dependent Manner ◽

Pancreatic Exocrine Secretion ◽

Pancreatic Exocrine ◽

Protein Output ◽

Dose Dependent ◽

Cck Release

In the present investigation, we have studied the effect of atropine on the pancreatic secretion stimulated by intraduodenal administration of either sodium oleate or exogenous cholecystokinin (CCK). In four dogs prepared with gastric and Thomas duodenal cannulas, pancreatic juice was collected for measurement of volume, bicarbonate, and protein output, and peripheral venous blood samples were obtained for radioimmunoassay of both secretin and CCK. Volume, bicarbonate, and protein output of the pancreatic juice increased significantly in response to sodium oleate (1-4 mmol/h) in a dose-dependent manner. The increase in pancreatic secretion paralleled the increments in both plasma CCK and secretin. Atropine given intravenously suppressed completely both pancreatic secretion and release of CCK stimulated by sodium oleate, whereas the release of secretin was not affected. Pancreatic secretion was significantly increased in a dose-dependent manner by exogenous CCK octapeptide (CCK-8) at 16, 32, and 64 micrograms (14, 28, and 56 pmol).kg-1.h-1. Atropine inhibited protein output only partially, but it did not influence bicarbonate output. In five additional dogs, the effect of atropine on L-tryptophan-stimulated pancreatic secretion was studied. Interestingly, atropine failed to influence the CCK release and pancreatic secretion of volume and bicarbonate, except for protein secretion, which was significantly inhibited. It was shown previously that atropine inhibited significantly the pancreatic secretion of bicarbonate stimulated by secretin in physiological doses. Thus we conclude that the inhibition by atropine of the pancreatic exocrine secretion stimulated by sodium oleate is mediated by both suppression of CCK release and inhibition of action of secretin on the exocrine pancreas.(ABSTRACT TRUNCATED AT 250 WORDS)

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

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1998.275.5.g957 ◽

1998 ◽

Vol 275 (5) ◽

pp. G957-G963 ◽

Cited By ~ 3

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.

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Cholecystokinin mediates feedback regulation of pancreatic enzyme secretion in rats

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1986.250.2.g252 ◽

1986 ◽

Vol 250 (2) ◽

pp. G252-G259 ◽

Cited By ~ 10

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.

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Chloride secretion and conductance of teleost opercular membrane: effects of prolactin

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1982.242.3.r380 ◽

1982 ◽

Vol 242 (3) ◽

pp. R380-R389 ◽

Cited By ~ 5

Author(s):

J. K. Foskett ◽

T. E. Machen ◽

H. A. Bern

Keyword(s):

Active Transport ◽

Short Circuit ◽

Chloride Secretion ◽

Alternative Interpretation ◽

Chloride Cells ◽

Dependent Manner ◽

Transport Pathway ◽

Accurate Analysis ◽

Equivalent Circuit Analysis ◽

Fish Yield

Effects of prolactin on transport properties of opercular membranes from seawater-adapted tilapia, Sarotherodon mossambicus, have been examined. These membranes are high conductance (average Gt approximately 4 mS.cm-2) tissues with short-circuit currents (I) equal to net chloride secretion. Despite high Gt, nonlinear current-voltage relationships suggest that opercular membranes cannot be classified as "leaky" tissues. Variability among membranes is reflected in a linear relationship between I and Gt with a slope equal to 26 mV and the zero-current Gt intercept equal to 0.45 mS.cm-2. Prolactin injections decrease I and Gt in a dose-dependent manner. Phosphodiesterase inhibition, without effect on I in untreated fish, often partially reverses these prolactin effects. Gt-I data from prolactin-treated fish yield a slope of 18 mV and a Gt intercept of 0.10 mS.cm-2. The effects of prolactin are discussed in terms of conventional equivalent circuit analysis. Discrepancies between predictions based on this model and the actual data indicate that an alternative interpretation, based on a heterogeneous cell population, is more accurate. Analysis of this circuit suggests that the ratio of paracellular to active transport pathway conductances associated with chloride cells is constant and that differences in Gt and I are due to parallel changes in these conductances. Prolactin may effectively "remove" chloride cells from these membranes as well as inhibit (reversible by elevated cellular cAMP levels) active transport pathway conductance of remaining cells.

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Signal Pathway in Salt-Activated Expression of the Salmonella Pathogenicity Island 1 Type III Secretion System in Salmonella enterica Serovar Typhimurium

Journal of Bacteriology ◽

10.1128/jb.01957-07 ◽

2008 ◽

Vol 190 (13) ◽

pp. 4624-4631 ◽

Cited By ~ 35

Author(s):

Hideaki Mizusaki ◽

Akiko Takaya ◽

Tomoko Yamamoto ◽

Shin-Ichi Aizawa

Keyword(s):

Electron Microscopy ◽

Real Time ◽

Protein Secretion ◽

Real Time Pcr ◽

Type Iii Secretion ◽

Type Iii Secretion System ◽

Secretion System ◽

Sds Page ◽

Two Component ◽

Serovar Typhimurium

ABSTRACT Salmonella enterica serovar Typhimurium secretes virulence factors for invasion called Sip proteins or Sips into its hosts through a type III secretion system (T3SS). In the absence of a host, S. enterica induces Sip secretion in response to sucrose or simple salts, such as NaCl. We analyzed induction of host-independent Sip secretion by monitoring protein secretion by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), assembly of needle complexes by electron microscopy, and transcription of virulence regulatory genes by quantitative reverse transcriptase PCR (real-time PCR). SDS-PAGE showed that addition of sucrose or simple salts, such as NaCl, to the growth medium induced Sip secretion without altering flagellar protein secretion, which requires a distinct T3SS. Electron microscopy confirmed that the amount of secreted Sips increased as the number of assembled needle complexes increased. Real-time PCR revealed that added sucrose or NaCl enhanced transcription of hilA, hilC, and hilD, which encode known regulators of Salmonella virulence. However, epistasis analysis implicated HilD and HilA, but not HilC, in the direct pathway from the salt stimulus to the Sip secretion response. Further analyses showed that the BarA/SirA two-component signal transduction pathway, but not the two-component sensor kinase EnvZ, directly activated hilD and hilA transcription and thus Sip secretion in response to either sucrose or NaCl. Finally, real-time PCR showed that salt does not influence transcription of the BarA/SirA-dependent csrB and csrC genes. A model is proposed for the major pathway in which sucrose or salt signals to enhance virulence gene expression.

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Vagally mediated, nonparacrine effects of cholecystokinin-8s on rat pancreatic exocrine secretion

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00118.2007 ◽

2007 ◽

Vol 293 (2) ◽

pp. G493-G500 ◽

Cited By ~ 18

Author(s):

Eddy Viard ◽

Zhongling Zheng ◽

Shuxia Wan ◽

R. Alberto Travagli

Keyword(s):

Brain Stem ◽

Protein Secretion ◽

Exocrine Secretion ◽

Vagal Afferents ◽

Dependent Manner ◽

Pancreatic Exocrine Secretion ◽

Sprague Dawley ◽

Pancreatic Exocrine ◽

Vagal Afferent

Cholecystokinin (CCK) has been proposed to act in a vagally dependent manner to increase pancreatic exocrine secretion via actions exclusively at peripheral vagal afferent fibers. Recent evidence, however, suggests the CCK-8s may also affect brain stem structures directly. We used an in vivo preparation with the aims of 1) investigating whether the actions of intraduodenal casein perfusion to increase pancreatic protein secretion also involved direct actions of CCK at the level of the brain stem and, if so, 2) determining whether, in the absence of vagal afferent inputs, CCK-8s applied to the dorsal vagal complex (DVC) can also modulate pancreatic exocrine secretion (PES). Sprague-Dawley rats (250–400 g) were anesthetized and the common bile-pancreatic duct was cannulated to collect PES. Both vagal deafferentation and pretreatment with the CCK-A antagonist lorglumide on the floor of the fourth ventricle decreased the casein-induced increase in PES output. CCK-8s microinjection (450 pmol) in the DVC significantly increased PES; the increase was larger when CCK-8s was injected in the left side of the DVC. Protein secretion returned to baseline levels within 30 min. Microinjection of CCK-8s increased PES (although to a lower extent) also in rats that underwent complete vagal deafferentation. These data indicate that, as well as activating peripheral vagal afferents, CCK-8s increases pancreatic exocrine secretion via an action in the DVC. Our data suggest that the CCK-8s-induced increases in PES are due mainly to a paracrine effect of CCK; however, a relevant portion of the effects of CCK is due also to an effect of the peptide on brain stem vagal circuits.

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