Postreceptor modulation of action of VIP and secretin on pancreatic enzyme secretion by secretagogues that mobilize cellular calcium

1982 ◽  
Vol 242 (4) ◽  
pp. G423-G428 ◽  
Author(s):  
M. J. Collen ◽  
V. E. Sutliff ◽  
G. Z. Pan ◽  
J. D. Gardner
Keyword(s):  
Vasoactive Intestinal Peptide ◽  
Pancreatic Enzyme ◽  
Enzyme Secretion ◽  
Secretory Process ◽  
Amylase Secretion ◽  
Pancreatic Acini ◽  
Rat Pancreas ◽  
Cellular Calcium ◽  
Twofold Increase ◽  
Pancreatic Enzyme Secretion

In dispersed acini from rat pancreas, secretagogues that act through or mimic the action of AMP [vasoactive intestinal peptide (VIP), secretin, or 8-bromo-AMP] caused a twofold increase in amylase secretion. Secretagogues that mobilize cellular calcium (carbamylcholine, C-terminal octapeptide of cholecystokinin, bombesin, or A23187) caused a sevenfold augmentation of the actions of VIP, secretin, or 8-bromo-cAMP on enzyme secretion. Carbamylcholine and the C-terminal octapeptide of cholecystokinin also augmented the action of VIP on amylase secretion from mouse pancreatic acini. Secretagogues that mobilize cellular calcium did not alter binding of 125I-VIP, cellular cAMP, or the increase in cellular cAMP caused by VIP or secretin. Similarly, secretagogues that increase cellular cAMP did not alter 45Ca outflux or the increase in 45Ca outflux caused by carbamylcholine, C-terminal octapeptide of cholecystokinin, bombesin, or A23187. These results indicate that in dispersed acini from rat pancreas there is postreceptor modulation of the actions of VIP and secretin on enzyme secretion by secretagogues that mobilize cellular calcium and that this modulation is a major determinant of the magnitude of the effect of VIP and secretin on enzyme secretion. This modulation, in turn, reflects the ability of cellular calcium, mobilized from intracellular stores, to amplify the action of cellular cAMP on the enzyme secretory process.

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.

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.

Receptors for vasoactive intestinal peptide and secretin on rat pancreatic acini

1984 ◽  
Vol 246 (6) ◽  
pp. G710-G717 ◽  
Author(s):  
B. M. Bissonnette ◽  
M. J. Collen ◽  
H. Adachi ◽  
R. T. Jensen ◽  
J. D. Gardner
Keyword(s):  
Vasoactive Intestinal Peptide ◽  
Binding Sites ◽  
Enzyme Secretion ◽  
Amylase Secretion ◽  
Temperature Dependent ◽  
Pancreatic Acini ◽  
Rat Pancreas ◽  
High Affinity ◽  
Fourth Class ◽  
Stimulation Of

In dispersed acini from rat pancreas, binding of 125I-labeled vasoactive intestinal peptide and 125I-labeled secretin was relatively rapid, reversible, saturable, and temperature dependent. The rate of dissociation of bound 125I-labeled peptide was not a function of the concentration of free vasoactive intestinal peptide or secretin, indicating that the apparent affinities of these labeled peptides for their binding sites do not depend on the extent of receptor occupation. Four classes of receptors are required to account for the actions of vasoactive intestinal peptide and secretin on enzyme secretion, cellular cAMP, and binding of 125I-vasoactive intestinal peptide and 125I-secretin. One class has a high affinity for vasoactive intestinal peptide, and occupation of this class of receptors causes increased cellular cAMP and stimulation of amylase secretion. A second class has a low affinity for vasoactive intestinal peptide and for secretin, and occupation of these receptors does not cause changes in cAMP or amylase secretion. A third class of receptors has a high affinity for secretin, and occupation of these receptors causes increased cAMP and stimulation of amylase secretion. A fourth class of receptors has a low affinity for secretin, and occupation of these receptors causes stimulation of amylase secretion by a non-cAMP-mediated mechanism.

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.

Cholecystokinin-induced desensitization of enzyme secretion in dispersed acini from guinea pig pancreas

1980 ◽  
Vol 239 (4) ◽  
pp. G272-G279 ◽  
Author(s):  
S. Abdelmoumene ◽  
J. D. Gardner
Keyword(s):  
Guinea Pig ◽  
Vasoactive Intestinal Peptide ◽  
Enzyme Secretion ◽  
Amylase Secretion ◽  
Temperature Dependent ◽  
Cellular Calcium ◽  
Maximal Stimulation ◽  
Stimulation Of

Incubating dispersed acini from guinea pig pancreas with cholecystokinin and then washing the cells to remove cholecystokinin reduced the subsequent stimulation of amylase secretion caused by pancreatic secretagogues, whose actions are mediated by release of cellular calcium (i.e., cholecystokinin, carbamylcholine, bombesin, litorin, physalaemin, and A23187), but did not alter the stimulation caused by secretagogues whose actions are mediated by cAMP (i.e., vasoactive intestinal peptide and secretin). This cholecystokinin-induced desensitization was reversible, and the onset of the process as well as its reversal were time- and temperature-dependent changes. The concentrations of cholecystokinin required to cause desensitization were greater than those required to cause maximal stimulation of amylase secretion, and this finding suggests that the submaximal stimulation of enzyme secretion seen with supramaximal concentrations of cholecystokinin may be caused by cholecystokinin-induced desensitization.

Cellular Calcium and Phospholipid Metabolism Mediate Pancreatic Enzyme Secretion

1990 ◽  
pp. 59-72 ◽  
Author(s):  
Stephen J. Pandol ◽  
Mari S. Shoeffield-Payne ◽  
Yalin Hsu ◽  
Peter E. Krims ◽  
Shmuel Muallem
Keyword(s):  
Pancreatic Enzyme ◽  
Phospholipid Metabolism ◽  
Enzyme Secretion ◽  
Cellular Calcium ◽  
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.

Action of natural glucagon on pancreatic acini: due to contamination by previously undescribed secretagogues

1983 ◽  
Vol 245 (5) ◽  
pp. G703-G710 ◽  
Author(s):  
S. J. Pandol ◽  
V. E. Sutliff ◽  
S. W. Jones ◽  
C. G. Charlton ◽  
T. L. O'Donohue ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Vasoactive Intestinal Peptide ◽  
Biologically Active ◽  
Enzyme Secretion ◽  
Amylase Secretion ◽  
Trypsin Treatment ◽  
Amylase Release ◽  
Pancreatic Acini ◽  
Maximal Stimulation ◽  
Threefold Increase

In dispersed acini from guinea pig pancreas, natural glucagon caused a two- to threefold increase in amylase secretion, and this natural glucagon-induced increase was augmented by theophylline. Natural glucagon also caused a sixfold increase in cellular cAMP but did not alter cellular cGMP or outflux of 45Ca. Natural glucagon caused detectable changes in cAMP and amylase secretion at a concentration of 1 microM, half-maximal stimulation at 10 microM, and maximal stimulation at 100 microM. Natural glucagon potentiated the increase in enzyme secretion caused by secretagogues that act by causing mobilization of cellular calcium but did not alter the increase in enzyme secretion caused by secretagogues that increase or mimic the action of cellular cAMP. At concentrations up to 100 microM, natural glucagon did not inhibit binding of 125I-vasoactive intestinal peptide. The potency with which glucagon stimulated amylase release and augmented the increase in amylase release caused by cholecystokinin or carbachol was the same with acini from rat or mouse pancreas as it was with acini from guinea pig pancreas. Biologically active synthetic glucagon did not increase enzyme secretion. On reverse-phase, high-pressure liquid chromatography of natural glucagon, the ability to stimulate enzyme secretion migrated differently from the glucagon. Natural glucagon, at concentrations that stimulated cAMP accumulation, did not react with vasoactive intestinal peptide or secretin radioimmunoassays. Neither insulin nor pancreatic polypeptide, which are known to contaminate natural glucagon preparations, increased enzyme secretion from pancreatic acini. Trypsin treatment abolished the ability of natural glucagon to increase enzyme secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Biochemical Reactions Involved in Pancreatic Enzyme Secretion. I. Activation of the Adenylate Cyclase Complex

1974 ◽  
Vol 52 (2) ◽  
pp. 174-182 ◽  
Author(s):  
A. R. Beaudoin ◽  
C. Marois ◽  
J. Dunnigan ◽  
J. Morisset
Keyword(s):  
Adenylate Cyclase ◽  
Pancreatic Enzyme ◽  
Pancreatic Tissue ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Enzyme Secretion ◽  
Amylase Secretion ◽  
Biochemical Reactions ◽  
Pancreatic Enzyme Secretion

Pancreatic amylase secretion was studied using an in vitro system. Secretion was increased by urecholine and cholecystokinin–pancreozymin (CCK–PZ). Addition of tetracaine and dibucaine to the medium abolished secretion stimulated by urecholine and decreased by 75% that stimulated by CCK–PZ. In contrast, an increase in enzyme secretion was observed after dibutyryl cyclic AMP; this was potentiated by tetracaine added to the medium. Oxygen uptake by pieces of pancreatic tissue was not affected by tetracaine. Adenylate cyclase activity, increased in vitro when CCK–PZ was added to a pancreas homogenate, was inhibited by 15% by tetracaine at 2 mM and by 67.5% at the 10 mM concentration.From data known on biochemical reactions associated with the process of secretion and the results described in the present paper, we propose a model for the activation of the pancreatic adenylate cyclase complex. Associated to the depolarization of the acinar cell plasma membrane by urecholine and CCK–PZ and an inward movement of sodium and calcium, there is an immediate rise in adenylate cyclase activity within 10 s which is timed with the initiation of amylase secretion.

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