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

1980 ◽  
Vol 238 (3) ◽  
pp. G213-G218
Author(s):  
P. C. Lee ◽  
R. T. Jensen ◽  
J. D. Gardner
Keyword(s):  
Protein Synthesis ◽  
Guinea Pig ◽  
Vasoactive Intestinal Peptide ◽  
Enzyme Secretion ◽  
Amylase Secretion ◽  
Temperature Dependent ◽  
Pancreatic Acini ◽  
Bombesin Receptor ◽  
Stimulation Of

Incubating dispersed acini from guinea pig pancreas with bombesin and then washing the cells to remove bombesin reduced the subsequent stimulation of amylase secretion caused by bombesin, litorin, or ranatensin by as much as 80%, but did not alter the stimulation of amylase secretion caused by cholecystokinin, carbamylcholine, A23187 or vasoactive intestinal peptide. This bombesin-induced desensitization was reversible, and the onset of the process, as well as its reversal, were time and temperature dependent. Neither desensitization or resensitization were inhibited by abolishing protein synthesis. The concentrations of bombesin required to cause desensitization were in the same range as those required to stimulate amylase secretion. Incubating pancreatic acini with vasoactive intestinal peptide did not reduce the subsequent stimulation of amylase secretion caused by vasoactive intestinal peptide, bombesin, or cholecystokinin. These results indicate that bombesin-induced desensitization of pancreatic acini reflects changes that occur at or close to the bombesin receptor.

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.

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.

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)

Action of theophylline on secretagogue-stimulated amylase release from dispersed pancreatic acini

1980 ◽  
Vol 239 (4) ◽  
pp. G324-G333
Author(s):  
L. Y. Korman ◽  
M. D. Walker ◽  
J. D. Gardner
Keyword(s):  
Guinea Pig ◽  
Vasoactive Intestinal Peptide ◽  
Enzyme Secretion ◽  
Amylase Release ◽  
Pancreatic Acini ◽  
Modes Of Action ◽  
Low Concentrations ◽  
High Concentrations ◽  
Stimulation Of

In dispersed acini from guinea pig pancreas, theophylline did not alter basal amylase release, but had three functionally distinct modes of action on the stimulation of amylase release caused by various secretagogues. 1) At relatively low concentrations (0.1-1.0 mM), theophylline augmented the increase in enzyme secretion caused by vasoactive intestinal peptide, secretin, or 8-bromoadenosine 3',5'-monophosphate, but did not alter the increase in amylase release caused by other secretagogues. 2) At intermediate concentrations (1-10 mM), theophylline selectively altered the increase in enzyme secretion caused by carbamylcholine, but did not alter the effects of cholecystokinin or bombesin, secretagogues whose modes of action are similar to that of cabamylcholine. 3) At high concentrations (greater than 10 mM), theophylline inhibited the increase in enzyme secretion caused by all secretagogues tested.

Actions of peptides isolated from amphibian skin on amylase release from dispersed pancreatic acini.

1979 ◽  
Vol 236 (5) ◽  
pp. E571
Author(s):  
E R Uhlemann ◽  
A J Rottman ◽  
J D Gardner
Keyword(s):  
Salivary Gland ◽  
Guinea Pig ◽  
Vasoactive Intestinal Peptide ◽  
Amylase Secretion ◽  
Amphibian Skin ◽  
Amylase Release ◽  
Pancreatic Acini ◽  
Stimulation Of

In dispersed acini prepared from guinea pig pancreas, peptides isolated from amphibian skin (caerulein, bombesin, litorin, and physalaemin) as well as eledoisin, a peptide isolated from the posterior salivary gland of a Mediterranean octopod, caused a significant increase in amylase release. Each amphibian peptide potentiated the stimulation of amylase release caused by vasoactive intestinal peptide or secretin in that the increase in amylase release caused by an amphibian peptide plus vasoactive intestinal peptide or secretin was significantly greater than the sum of the increase caused by each secretagogue acting alone. Potentiation of amylase secretion did not occur with an amphibian peptide plus cholecystokinin or carbachol.

Structural requirements for action of cholecystokinin on enzyme secretion from pancreatic acini

1982 ◽  
Vol 242 (4) ◽  
pp. G416-G422 ◽  
Author(s):  
M. L. Villanueva ◽  
S. M. Collins ◽  
R. T. Jensen ◽  
J. D. Gardner
Keyword(s):  
Guinea Pig ◽  
Enzyme Secretion ◽  
Amylase Secretion ◽  
Structural Requirements ◽  
Pancreatic Acini ◽  
Relative Potencies ◽  
Stimulation Of

Using dispersed acini prepared from guinea pig pancreas, we found that the structural requirements for cholecystokinin-induced stimulation of amylase secretion are the same as those for cholecystokinin-induced desensitization of amylase secretion. 1) The relative potencies with which various C-terminal fragments of cholecystokinin cause stimulation are the same as their relative potencies for causing desensitization. 2) With each fragment tested, desensitization occurs with peptide concentrations that are supramaximal for causing stimulation of amylase secretion. 3) Fragments of cholecystokinin less efficacious in causing supramaximal inhibition of amylase secretion are also less efficacious in causing desensitization of amylase secretion. In contrast, there is no obvious fixed relation between the ability of a cholecystokinin fragment to cause stimulation of enzyme secretion and its ability to cause residual stimulation of enzyme secretion. Cholecystokinin and its C-terminal hexadecapeptide are 25-40% more efficacious than the C-terminal decapeptide, octapeptide, and heptapeptide in causing residual stimulation, and the C-terminal pentapeptide and tetrapeptide caused no detectable residual stimulation. The C-terminal tetrapeptide, however, can prevent as well as reverse the residual stimulation caused by other cholecystokinin fragments, and the ability of the tetrapeptide to prevent cholecystokinin-induced residual stimulation is itself fully reversible.

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.

Discovery of a cholecystokinin analogue with partial agonist activity

1984 ◽  
Vol 247 (3) ◽  
pp. G261-G264 ◽  
Author(s):  
J. M. Howard ◽  
M. Knight ◽  
R. T. Jensen ◽  
J. D. Gardner
Keyword(s):  
Guinea Pig ◽  
Partial Agonist ◽  
Effective Concentration ◽  
Amylase Secretion ◽  
Agonist Activity ◽  
Pancreatic Acini ◽  
Rat Pancreas ◽  
Partial Agonist Activity ◽  
Stimulation Of

In dispersed acini from guinea pig pancreas, cholecystokinin-(27-32)-amide [CCK-(27-32)-NH2] did not stimulate amylase secretion and inhibited the stimulation caused by CCK-(26-33). In dispersed acini from mouse or rat pancreas, CCK-(27-32)-NH2 stimulated amylase secretion. The stimulation of amylase secretion caused by a maximally effective concentration of CCK-(27-32)-NH2 was less than that caused by a maximally effective concentration of cholecystokinin-(26-33), and in contrast to the action of cholecystokinin-(26-33) supramaximal concentrations of CCK-(27-32)-NH2 did not cause submaximal stimulation of amylase secretion. Dibutyryl cGMP and proglumide each inhibited the stimulation of amylase secretion caused by CCK-(27-32)-NH2. CCK-(27-32)-NH2 inhibited binding of 125I-labeled CCK to mouse and rat pancreatic acini. These results indicate that, in mouse and rat pancreatic acini, CCK-(27-32)-NH2 is a partial agonist and that this partial agonist activity is produced by occupation of the CCK receptor by CCK-(27-32)-NH2.

Cholecystokinin-induced persistent stimulation of enzyme secretion from pancreatic acini

1981 ◽  
Vol 240 (6) ◽  
pp. G459-G465 ◽  
Author(s):  
S. M. Collins ◽  
S. Abdelmoumene ◽  
R. T. Jensen ◽  
J. D. Gardner
Keyword(s):  
Enzyme Secretion ◽  
Amylase Secretion ◽  
Intermediate Step ◽  
Pancreatic Acini ◽  
Persistent Effect ◽  
Incubation Solution ◽  
Cholecystokinin Receptors ◽  
Incomplete Removal ◽  
High Concentrations ◽  
Stimulation Of

When pancreatic acini are first incubated with cholecystokinin, washed to remove free cholecystokinin and then reincubated in fresh incubation solution, there is significant residual stimulation of amylase secretion. This residual stimulation requires relatively high concentrations of the secretagogue, is reversible, and is specific for cholecystokinin. Induction of residual stimulation occurs more rapidly at 37 degrees C (maximal by 1 min) than at 4 degrees C (maximal by 10 min), and, once induced, residual stimulation persists for up to 75 min at 37 degrees C and for more than 90 min at 4 degrees C. The persistent effect of cholecystokinin on enzyme secretion cannot be accounted for by incomplete removal of the secretagogue by the wash procedure or by activation of some intermediate step in the mechanism of action of cholecystokinin that persists after the secretagogue dissociates from its receptors. Instead, cholecystokinin-induced residual stimulation of enzyme secretion appears to result from persistent occupation of cholecystokinin receptors by the secretagogue.

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.

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