Cholecystokinin-induced restricted stimulation of pancreatic enzyme secretion

1982 ◽  
Vol 242 (5) ◽  
pp. G464-G469 ◽  
Author(s):  
N. Barlas ◽  
R. T. Jensen ◽  
J. D. Gardner
Keyword(s):  
Dose Response ◽  
Incubation Time ◽  
Response Curve ◽  
Pancreatic Enzyme ◽  
Enzyme Secretion ◽  
Enzyme Release ◽  
Pancreatic Acini ◽  
Basal Rate ◽  
Pancreatic Enzyme Secretion ◽  
Stimulation Of

During a 5-min incubation with increasing concentrations of cholecystokinin, enzyme secretion from pancreatic acini increased, became maximal at 1 nM cholecystokinin, and then decreased progressively to 65% of maximal with concentrations of cholecystokinin above 1 nM. During a 20-min incubation with increasing concentrations of cholecystokinin, enzyme secretion increased, became maximal at 0.3 nM cholecystokinin, and then decreased progressively to 40% of maximal with concentrations of cholecystokinin above 0.3 nM. The configuration of the dose-response curve for cholecystokinin-stimulated enzyme secretion did not change when the incubation time was increased from 20 to 30, 45, or 60 min. Concentrations of cholecystokinin that were supramaximal for stimulating enzyme secretion abolished the stimulation caused by other secretagogues that promote mobilization of cellular calcium (e.g., carbamylcholine, bombesin, physalaemin, or A23187), as well as that caused by secretagogues that elevate cellular cAMP (e.g., vasoactive intestinal peptide or secretin). The submaximal stimulation caused by supramaximal concentrations of cholecystokinin reflects what we have termed "restricted stimulation" of enzyme secretion. Secretion is than the basal rate of release and is "restricted" in the sense that enzyme release is submaximal and cannot be increased by adding another secretagogue.

Effects of inhibitors of cyclic nucleotide phosphodiesterase on actions of cholecystokinin, bombesin, and carbachol on pancreatic acini

1983 ◽  
Vol 245 (5) ◽  
pp. G676-G680
Author(s):  
J. D. Gardner ◽  
V. E. Sutliff ◽  
M. D. Walker ◽  
R. T. Jensen
Keyword(s):  
Dose Response ◽  
Cyclic Nucleotide ◽  
Response Curve ◽  
Dose Response Curve ◽  
Cyclic Nucleotide Phosphodiesterase ◽  
Enzyme Secretion ◽  
Amylase Secretion ◽  
Pancreatic Acini ◽  
Rightward Shift ◽  
Stimulation Of

In dispersed acini from guinea pig pancreas two inhibitors of cyclic nucleotide phosphodiesterase, Ro 20-1724 and 3-isobutyl-1-methylxanthine (IBMX), augmented the increase in amylase secretion caused by supramaximal concentrations of cholecystokinin but did not alter the stimulation of enzyme secretion caused by bombesin. The augmentations of the action of cholecystokinin caused by Ro 20-1724 or IBMX could be reproduced by 8-bromo-cAMP. When tested alone or with theophylline, cholecystokinin did not alter cAMP in pancreatic acini; however, with Ro 20-1724 or IBMX, concentrations of cholecystokinin that were supramaximal for stimulating amylase secretion caused a significant increase in cellular cAMP. These findings indicate that Ro 20-1724 and IBMX augment the action of cholecystokinin on enzyme secretion by inhibiting cyclic nucleotide phosphodiesterase and allowing a significant cholecystokinin-induced increase in cellular cAMP. IBMX but not Ro 20-1724 caused a parallel rightward shift in the dose-response curve for the stimulation of amylase secretion caused by carbachol. IBMX also caused a parallel rightward shift in the dose-response curve for the stimulation of outflux of 45Ca caused by carbachol. These results indicate that IBMX, but not Ro 20-1724, can function as a muscarinic cholinergic antagonist.

Selective modification of the ability of cholecystokinin to cause residual stimulation of pancreatic enzyme secretion

1982 ◽  
Vol 243 (3) ◽  
pp. G214-G217
Author(s):  
M. L. Villanueva ◽  
J. Martinez ◽  
M. Bodanszky ◽  
S. M. Collins ◽  
R. T. Jensen ◽  
...  
Keyword(s):  
Aspartic Acid ◽  
Pancreatic Enzyme ◽  
Terminal Region ◽  
Enzyme Secretion ◽  
Aspartic Acid Residue ◽  
Pancreatic Acini ◽  
Pancreatic Enzyme Secretion ◽  
Stimulation Of

In the C-terminal heptapeptide of cholecystokinin (-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2), replacing the aspartic acid residue by beta-aspartic acid did not alter the ability of the peptide to cause stimulation, desensitization, or residual stimulation of enzyme secretion from dispersed pancreatic acini. Replacing the tyrosine sulfate residue by hydroxynorleucine sulfate did not alter the ability of the heptapeptide to cause stimulation or desensitization, but caused a 50-fold decrease in the potency with which the peptide caused residual stimulation of enzyme secretion. These findings suggest that a modification of the N-terminal region of cholecystokinin heptapeptide, which does not alter the ability of the peptide to bind to its receptor on pancreatic acini and by so doing cause stimulation and desensitization of enzyme secretion, can increase the rate at which the bound peptide dissociates when the acini are washed and reincubated. This increased dissociation is reflected by a reduction in the potency with which the peptide causes residual stimulation of enzyme secretion.

Reversal of cholecystokinin-induced persistent stimulation of pancreatic enzyme secretion by dibutyryl cyclic GMP

1981 ◽  
Vol 240 (6) ◽  
pp. G466-G471 ◽  
Author(s):  
S. M. Collins ◽  
S. Abdelmoumene ◽  
R. T. Jensen ◽  
J. D. Gardner
Keyword(s):  
Cyclic Gmp ◽  
Pancreatic Enzyme ◽  
Enzyme Secretion ◽  
Amylase Secretion ◽  
Pancreatic Acini ◽  
Incubation Solution ◽  
Complete Reversal ◽  
Pancreatic Enzyme Secretion ◽  
Derivatives Of ◽  
Stimulation Of

When pancreatic acini are first incubated with cholecystokinin, washed to remove free cholecystokinin, and then reincubated in fresh incubation solution, there is a significant residual stimulation of amylase secretion. Butyryl derivatives of cyclic GMP can prevent as well as reverse this cholecystokinin-induced residual stimulation. At 37 degrees C the nucleotide-induced reversal is complete within a few minutes, but at 4 degrees C complete reversal requires 90 min of incubation. The ability of butyryl cyclic GMP to reverse cholecystokinin-induced residual stimulation is itself fully reversible, and the nucleotide-induced reversal is accompanied by restoration of full responsiveness to cholecystokinin. The ability of dibutyryl cyclic GMP to reverse cholecystokinin-induced residual stimulation appears to result from the ability of the nucleotide to displace cholecystokinin from its receptors in pancreatic acini.

Direct demonstration of increases in cytosolic free Ca2+ during stimulation of pancreatic enzyme secretion

1983 ◽  
Vol 3 (3) ◽  
pp. 233-240 ◽  
Author(s):  
R. L. Dormer
Keyword(s):  
Divalent Cation ◽  
Pancreatic Enzyme ◽  
Enzyme Secretion ◽  
Ionophore A23187 ◽  
Pancreatic Acini ◽  
Direct Demonstration ◽  
Pancreatic Enzyme Secretion ◽  
Hypotonic Swelling ◽  
Isolated Rat ◽  
Stimulation Of

The Ca2+-activated photoprotein aequorin has been incorporated into intact, isolated rat pancreatic acini by a hypotonic swelling method. The isolated acini retained normal secretory responses after loading with aequorin. Increases in cytosolic Ca2+ concentration in response to a physiological secretagogue, carbamylcholine, and to divalent-cation ionophore A23187 have been demonstrated. Simultaneous measurement of the dynamics of enzyme secretion and changes in cytosolic Ca2+ concentration has been achieved using a newly developed apparatus.

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.

Stimulation of Pancreatic Enzyme Secretion by a Peptide Purified from Rat Bile-Pancreatic Juice

1986 ◽  
Vol 116 (8) ◽  
pp. 1540-1546 ◽  
Author(s):  
Shin-Ichi Fukuoka ◽  
Masahiro Tsujikawa ◽  
Tohru Fushiki ◽  
Kazuo Iwai
Keyword(s):  
Pancreatic Juice ◽  
Pancreatic Enzyme ◽  
Enzyme Secretion ◽  
Pancreatic Enzyme Secretion ◽  
Rat Bile ◽  
Stimulation Of

Effect of extracellular calcium on amylase release from dispersed pancreatic acini.

1979 ◽  
Vol 236 (6) ◽  
pp. E754
Author(s):  
J D Gardner ◽  
C L Costenbader ◽  
E R Uhlemann
Keyword(s):  
Guinea Pig ◽  
Vasoactive Intestinal Peptide ◽  
Cyclic Nucleotides ◽  
Extracellular Calcium ◽  
Enzyme Release ◽  
Amylase Release ◽  
Pancreatic Acini ◽  
Basal Rate ◽  
Derivatives Of ◽  
Stimulation Of

In dispersed acini prepared from guinea pig pancreas, removing extracellular calcium did not alter the basal rate of amylase release but reduced the stimulation of enzyme release caused by cholecystokinin, carbachol, secretin, and vasoactive intestinal peptide as well as that caused by derivatives of cyclic nucleotides. In acini incubated in a calcium-free, EGTA-containing medium the increase in amylase release caused by each secretagogue tested did not change during the initial 10 min of incubation, decreased by approximately 65% during the subsequent 40 min, and remained constant thereafter. Removing extracellular calcium did not alter the maximally effective concentrations of cholecystokinin or vasoactive intestinal peptide but abolished the decrease in stimulated enzyme secretion seen with supramaximal concentrations of cholecystokinin. Incubating pancreatic acini with cholecystokinin or carbachol plus secretin or vasoactive intestinal peptide caused potentiation of amylase release, and removing extracellular calcium reduced the stimulation of enzyme release caused by the two secretagogues in combination but did not alter their potentiating interactions.

Prostaglandin E2 inhibits secretagogue-induced enzyme secretion from rat pancreatic acini

1991 ◽  
Vol 260 (5) ◽  
pp. G711-G719
Author(s):  
J. Mossner ◽  
R. Secknus ◽  
G. M. Spiekermann ◽  
C. Sommer ◽  
M. Biernat ◽  
...  
Keyword(s):  
Prostaglandin E2 ◽  
Pancreatic Enzyme ◽  
Enzyme Secretion ◽  
Amylase Secretion ◽  
Binding Studies ◽  
Pancreatic Acini ◽  
Inositol 1,4,5 Trisphosphate ◽  
Pancreatic Enzyme Secretion ◽  
Hcl Secretion ◽  
Specific Receptors

Prostaglandins of the E type may have a potential role in pancreatic physiology and pathophysiology. Because prostaglandins of the E type inhibit HCl secretion in parietal cells via a specific receptor by inhibition of adenylylcyclase, we studied whether a similar mechanism exists in the exocrine pancreas. Isolated rat pancreatic acini were incubated with various concentrations of secretagogues, such as cholecystokinin-octapeptide (CCK-8), bombesin, carbachol, and vasoactive intestinal peptide (VIP), in the absence or presence of prostaglandin E2 (PGE2), and amylase secretion was measured. For receptor binding studies, acini and pancreatic membranes were incubated with [3H]PGE2 and either unlabeled PGE2 or other types of prostaglandins. PGE2 (10(-13) to 10(-5) M) did not inhibit basal amylase secretion. However, CCK-8-stimulated secretion was significantly inhibited. Stimulation of secretion by bombesin, carbachol, VIP, and secretin was also inhibited by PGE2, but not as pronounced as CCK-8-stimulated secretion. The formation of inositol 1,4,5-trisphosphate induced by CCK-8 was markedly inhibited by simultaneous incubation with PGE2. Furthermore, PGE2 slightly but significantly reduced the CCK-8-induced efflux of 45Ca2+ from prelabeled acini. Intact acini and a membrane fraction bound [3H]PGE2 and this function could be equally competed by either unlabeled PGE2 or PGE1 in contrast to less-related prostaglandins such as PGF2 alpha, PGD2, and prostacyclin. We conclude that prostaglandins of the E type inhibit pancreatic enzyme secretion stimulated by various secretagogues. This function is mediated via specific receptors for PGE. With regard to CCK-8-stimulated secretion this function may be mediated by an inhibition of formation of inositol 1,4,5-trisphosphate.

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