scholarly journals The inhibitory effect of CR-1409 on amylase secretion and intracellular Ca2+ mobilization in rat pancreatic acini in vitro.

1989 ◽  
Vol 39 (4) ◽  
pp. 585-593 ◽  
Author(s):  
Hirotsugu SHINOZAKI ◽  
Akihiro FUNAKOSHI ◽  
Hideyuki WAKASUGI ◽  
Muneaki ABE
Keyword(s):  
Inhibitory Effect ◽  
Amylase Secretion ◽  
Pancreatic Acini

Effects of synthetic cyclic AMP analogs on amylase exocytosis from rat pancreatic acini

1994 ◽  
Vol 72 (10) ◽  
pp. 1138-1147 ◽  
Author(s):  
Claus Schäfer ◽  
Hanna Steffen ◽  
Hartmut Printz ◽  
Burkhard Göke
Keyword(s):  
Protein Kinases ◽  
Vasoactive Intestinal Polypeptide ◽  
Inhibitory Effect ◽  
Amylase Secretion ◽  
Amylase Release ◽  
Pancreatic Acini ◽  
Dependent Protein ◽  
Maximal Induction ◽  
Intestinal Polypeptide

Diastereomers of adenosine 3′,5′-phosphorothioate activate cAMP-dependent protein kinases (cAMP-PK) in vitro. We found that these compounds are highly selective tools to monitor cAMP-dependent PKA activation and its effect on amylase exocytosis from pancreatic acini. In permeabilized rat acinar cells, (Sp)-cAMPS dose-dependently stimulated amylase secretion, while (Rp)-cAMPS inhibited (Sp)-cAMPS-induced amylase release. In intact rat acini, 8-Br-(Sp)-cAMPS reduced the secretory responses to secretin, vasoactive intestinal polypeptide (VIP), 8-Br-cAMP, and 8-Br-(Sp)-cAMPS, but not to cerulein. Another derivative, dibutyryl-(Rp)-cAMPS, induced a small inhibitory effect against 8-Br-(Sp)-cAMPS and VIP, which was overlapped by an unspecific stimulatory effect on amylase exocytosis induced by the degradation product butyrate. Furthermore, (Sp)-5,6-dichloro-1-β-D-ribofuranosylbenzimidazole-3′,5′-monophosphorothioate ((Sp)-5,6-DCl-cBIMPS), a specific cAMP-PK activator, induced a maximal induction of cAMP-PK activity, but its stimulation of amylase secretion was less than that by secretin. (Sp)-5,6-DCl-cBIMPS regulated the phosphorylation of several proteins, which were also affected by secretin. However, secretin had additional effects. Its action was most likely mediated by a dual effect on the cAMP and the calcium pathway. Our results indicate that the cAMP-dependent pathway is involved in amylase exocytosis from rat pancreatic acini.Key words: secretin, vasoactive intestinal polypeptide, (Rp)-cAMPS, (Sp)-cAMPS, 8-Br-(Rp)-cAMPS, 8-Br-(Sp)-cAMPS, dibutyryl-(Rp)-cAMPS, (Sp)-5,6-DCl-cBIMPS, cAMP-dependent protein kinases, pancreatic acini, amylase secretion.

A new biological contribution of cyclo(His-Pro) to the peripheral inhibition of pancreatic secretion

1997 ◽  
Vol 273 (6) ◽  
pp. E1127-E1132 ◽  
Author(s):  
Pascal Fragner ◽  
Olivier Presset ◽  
Nicole Bernad ◽  
Jean Martinez ◽  
Claude Roze ◽  
...  
Keyword(s):  
Pancreatic Secretion ◽  
Biological Activities ◽  
Systemic Circulation ◽  
Inhibitory Effect ◽  
Pancreatic Acinar Cells ◽  
Exocrine Pancreatic Secretion ◽  
Amylase Release ◽  
Pancreatic Acini

The tripeptide pyro-Glu-His-Pro-NH2[thyrotropin-releasing hormone (TRH)] was isolated from the hypothalamus as a thyrotropin-releasing factor. It has a broad spectrum of central nervous system-mediated actions, including the stimulation of exocrine pancreatic secretion. TRH is also synthesized in the endocrine pancreas and found in the systemic circulation. Enzymatic degradation of TRH in vivo produces other bioactive peptides such as cyclo(His-Pro). Because of the short half-life of TRH and the stability of cyclo(His-Pro) in vivo, we postulated that at least part of the peripheral TRH effects on the exocrine pancreatic secretion may be attributed to cyclo(His-Pro), which has been shown to have other biological activities. This study determines in parallel the peripheral effects of TRH and cyclo(His-Pro) as well as the putative contribution of other TRH-related peptides on exocrine pancreatic secretion in rats. TRH and its metabolite cyclo(His-Pro) dose dependently inhibited 2-deoxy-d-glucose (2-DG)-stimulated pancreatic secretion. TRH and all the related peptides tested had no effect on the basal and cholecystokinin-stimulated amylase release from pancreatic acinar cells in vitro. These data indicate that cyclo(His-Pro) mimics the peripheral inhibitory effect of TRH on 2-DG-stimulated exocrine pancreatic secretion. This effect is not detected on isolated pancreatic acini. Our findings provide a new biological contribution for cyclo(His-Pro) with potential experimental and clinical applications.

scholarly journals Morphometric Measurements to Quantify the Cerulein Induced Hyperstimulatory Pancreatitis of Rats under the Protective Effect of Lectins

1998 ◽  
Vol 17 (4) ◽  
pp. 219-230 ◽  
Author(s):  
Ludwig Jonas ◽  
Ulrike Mikkat ◽  
Anke Witte ◽  
Uta Beckmann ◽  
Katrin Dölker ◽  
...  
Keyword(s):  
Protective Effect ◽  
Amylase Activity ◽  
Acinar Cells ◽  
Inhibitory Effect ◽  
Pancreatic Acinar Cells ◽  
Amylase Secretion ◽  
Ulex Europaeus ◽  
Serum Amylase Activity

In preceding papers we demonstrated an inhibitory effect of wheat germ agglutinin (WGA) and Ulex europaeus agglutinin (UEA) on the cholecystokinin (CCK) binding to the CCK receptor of rat pancreatic cells and also on the CCK induced Ca2+release and α-amylase secretionin vitroas well as on pancreatic secretion of intact ratsin vivo. In the present study we show the same inhibitory effect of both lectins on the cerulein pancreatitis of rats. This acute pancreatitis was induced by supramaximal injections (5 µg/kg/h iv or 10 µg/kg/h ip) of the CCK analogue cerulein in rats every hour. To monitor the degree of pancreatitis, we measured the number and diameter of injury vacuoles in the pancreatic acinar cells as one of the most important signs of this type of pancreatitis by light microscopic morphometry with two different systems on paraffin sections. Furthermore, the serum α-amylase activity was measured biochemically. We found a correlation between the diameter of vacuoles inside the acinar cells and the serum enzyme activity up to 24 h. The simultaneous ip administration of cerulein and WGA or UEA in a dosage of 125 µg/kg/h for 8 h led to a reduction of vacuolar diameter from 13.1 ± 2.0 µm (cerulein) to 7.5 ± 1.1 µm (cerulein + WGA) or 7.2 ± 1.3 µm (cerulein + UEA). The serum amylase activity was reduced from 63.7 ± 15.8 mmol/l \times min (cerulein) to 37.7 ± 11.8 (cerulein + WGA) or 39.4; +52.9; -31.1 (cerulein + UEA-I). Both parameters allow the grading this special type of pancreatitis to demonstrate the protective effect of the lectins.

Amylase Secretion from Dispersed Human Pancreatic Acini: Neither Cholecystokinin A Nor Cholecystokinin B Receptors Mediate Amylase Secretion In Vitro

Pancreas ◽  
2002 ◽  
Vol 25 (2) ◽  
pp. 161-165 ◽  
Author(s):  
Kyoko Miyasaka ◽  
Hirotsugu Shinozaki ◽  
Atsuo Jimi ◽  
Akihiro Funakoshi
Keyword(s):  
Amylase Secretion ◽  
Pancreatic Acini

Ethanol differentially regulates NF-κB activation in pancreatic acinar cells through calcium and protein kinase C pathways

2004 ◽  
Vol 286 (2) ◽  
pp. G204-G213 ◽  
Author(s):  
Anna S. Gukovskaya ◽  
Saeed Hosseini ◽  
Akihiko Satoh ◽  
Jason H. Cheng ◽  
Kyung J. Nam ◽  
...  
Keyword(s):  
Acinar Cells ◽  
Inhibitory Effect ◽  
Pancreatic Acinar Cells ◽  
Alcoholic Pancreatitis ◽  
Pancreatic Acini ◽  
Intracellular Ca ◽  
Ethanol Feeding ◽  
Ethanol Ethanol

Mechanisms of alcoholic pancreatitis remain unknown. Previously, we showed that ethanol feeding sensitizes rats to pancreatitis caused by CCK-8, at least in part, by augmenting activation of the proinflammatory transcription factor NF-κB. To elucidate the mechanism of sensitization, here we investigate the effect of ethanol on Ca2+- and PKC-mediated pathways of CCK-induced NF-κB activation using an in vitro system of rat pancreatic acini incubated with ethanol. Ethanol augmented CCK-8-induced activation of NF-κB, similar to our in vivo findings with ethanol-fed rats. In contrast, ethanol prevented NF-κB activation caused by thapsigargin, an agent that mobilizes intracellular Ca2+ bypassing the receptor. Pharmacological analysis showed that NF-κB activation by thapsigargin but not by CCK-8 is mediated through the calcineurin pathway and that the inhibitory effect of ethanol on the thapsigargin-induced NF-κB activation could be through inhibiting this pathway. Ethanol augmented NF-κB activation induced by the phorbol ester PMA, a direct activator of PKC. Inhibitory analysis demonstrated that Ca2+-independent (novel and/or atypical) PKC isoforms are involved in NF-κB activation induced by both CCK-8 and PMA in cells treated and not treated with ethanol. The results indicate that ethanol differentially affects the Ca2+/calcineurin- and PKC-mediated pathways of NF-κB activation in pancreatic acinar cells. These effects may play a role in the ability of ethanol to sensitize pancreas to the inflammatory response and pancreatitis.

Carbachol regulates cholecystokinin receptor on pancreatic acinar cells

1987 ◽  
Vol 252 (1) ◽  
pp. G77-G83
Author(s):  
T. Honda ◽  
H. Adachi ◽  
M. Noguchi ◽  
S. Sato ◽  
S. Onishi ◽  
...  
Keyword(s):  
Binding Sites ◽  
Calcium Ionophore ◽  
Inhibitory Effect ◽  
Calcium Ionophore A23187 ◽  
Pancreatic Acinar Cells ◽  
Amylase Secretion ◽  
Ionophore A23187 ◽  
Pancreatic Acini ◽  
Cholecystokinin Receptor ◽  
Apparent Loss

We have examined the effect of carbamylcholine on the binding of cholecystokinin (CCK) to dispersed acini from rat pancreas. The CCK receptor on pancreatic acini possesses two classes of binding sites. Simultaneous addition of carbamylcholine inhibited binding of CCK to acini due to an apparent loss of high affinity CCK binding sites. Atropine prevented the inhibitory effect of carbamylcholine, whereas calcium ionophore A23187 did not alter binding of CCK. 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibited binding of CCK in the same manner as carbamylcholine. Inhibition by carbamylcholine was reversible and the recovery was time dependent. By contrast, inhibition of binding of CCK by TPA did not reverse after a 60-min incubation without the agent. These findings, at least in part, account for the inhibition of the CCK-induced stimulation of amylase secretion by carbamylcholine. The action of TPA on binding of CCK suggests the possible involvement of the activation of protein kinase C in the inhibition of binding.

Comparative effects of CCK receptor antagonists on rat pancreatic secretion in vivo

1989 ◽  
Vol 256 (1) ◽  
pp. G150-G157 ◽  
Author(s):  
M. Niederau ◽  
C. Niederau ◽  
G. Strohmeyer ◽  
J. H. Grendell
Keyword(s):  
Pancreatic Secretion ◽  
Rank Order ◽  
Amylase Secretion ◽  
Receptor Antagonists ◽  
Pancreatic Acini ◽  
Cck Receptors ◽  
Competitive Kinetics ◽  
Cck Receptor Antagonists

The present experiments evaluate in vivo effects of recently described cholecystokinin (CCK) receptor antagonists on rat pancreatic secretion. Pancreaticobiliary secretion was studied after bile duct cannulation in anesthetized rats. After two basal 10-min fractions were selected, secretion was stimulated by intravenous caerulein (0.1-30.0 micrograms/kg) or secretin, and collected for seven further 10-min fractions. Peptide antagonists (CR 1409, CR 1392, and CR 1505) and nonpeptide antagonists (asperlicin and L364,718) were given intravenously 10 min before agonists. Increasing doses of antagonists gradually reduced secretion of protein and enzymes stimulated by submaximal and maximal doses of caerulein. The antagonists did not alter nonstimulated or secretin-stimulated secretion, indicating their specificity for the CCK receptor. Except for proglumide and asperlicin, all antagonists were able to abolish caerulein-stimulated pancreatic secretion, as evaluated by the mean integrated 1-h response to a near-maximal dose of caerulein. The caerulein dose-response curve was gradually shifted to the right by increasing doses of CR 1409, indicating competitive-like kinetics. Inhibition of secretion due to supramaximal doses of caerulein, however, could be reversed by doses of CR 1409 smaller than expected from extrapolating truely competitive kinetics from an in vitro situation to the in vivo situation. The rank order of potency of the compounds to antagonize caerulein-stimulated secretion in vivo agreed with their relative potencies to antagonize caerulein-stimulated amylase secretion from pancreatic acini in vitro as well as with their affinity to bind to peripheral CCK receptors in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals On the protective mechanisms of nitric oxide in acute pancreatitis

Gut ◽  
1998 ◽  
Vol 43 (3) ◽  
pp. 401-407 ◽  
Author(s):  
J Werner ◽  
C Fernández-del Castillo ◽  
J A Rivera ◽  
N Kollias ◽  
K B Lewandrowski ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Acute Pancreatitis ◽  
No Synthase ◽  
Amylase Secretion ◽  
Capillary Perfusion ◽  
No Donor ◽  
Pancreatic Acini ◽  
No Donors ◽  
Trypsinogen Activation

Background—Ectopic protease activation, microcirculatory changes, and leucocyte activation are the main events in the pathogenesis of acute pancreatitis. Nitric oxide (NO) is known to be a key mediator in the normal and inflamed pancreas.Aims—To investigate the targets on which NO exerts its effect in caerulein induced pancreatitis.Methods—Acute pancreatitis was induced in rats which additionally received either the NO synthase substrate, l-arginine; the NO donor, sodium nitroprusside; or the NO synthase inhibitor, N-nitro-l-arginine methyl ester (l-NAME). At six hours, pancreatic injury (oedema, leucocyte content, ectopic trypsinogen activation) was analysed and pancreatic oxygenation and perfusion were determined. A direct influence of NO on amylase secretion and trypsinogen activation was evaluated separately in vitro.Results—Both NO donors reduced the grade of inflammation. l-NAME increased the severity of inflammation, while decreasing pancreatic tissue oxygenation. Although neither amylase secretion nor intracellular trypsinogen activation in caerulein stimulated pancreatic acini was influenced by either NO donors or inhibitors, both NO donors decreased intrapancreatic trypsinogen activation peptide (TAP) and pancreatic oedema in vivo, andl-NAME increased TAP.Conclusions—NO protects against injury caused by pancreatitis in the intact animal but has no discernible effect on isolated acini. It is likely that in pancreatitis NO acts indirectly via microcirculatory changes, including inhibition of leucocyte activation and preservation of capillary perfusion.

Factors regulating amylase secretion from chicken pancreatic acini in vitro

Life Sciences ◽  
2000 ◽  
Vol 66 (7) ◽  
pp. 585-591 ◽  
Author(s):  
Atsushi Murai ◽  
Say Satoh ◽  
Jun-ichi Okumura ◽  
Mitsuhiro Furuse
Keyword(s):  
Amylase Secretion ◽  
Pancreatic Acini

Characterization of a new CCK antagonist, L364,718: in vitro and in vivo studies

1988 ◽  
Vol 255 (3) ◽  
pp. G261-G266 ◽  
Author(s):  
D. S. Louie ◽  
J. P. Liang ◽  
C. Owyang
Keyword(s):  
Pancreatic Juice ◽  
Competitive Inhibition ◽  
In Vivo Studies ◽  
Amylase Secretion ◽  
Receptor Antagonists ◽  
Amylase Release ◽  
Pancreatic Acini ◽  
Cck Antagonist

In this study we examined a novel, orally effective, nonpeptidal cholecystokinin (CCK) antagonist, 3S(-)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepine-3-yl) -1H-indole-2-carboxamide (L364,718) on CCK-induced amylase release. We used isolated rat pancreatic acini and incubated them with CCK-8 with or without various CCK receptor antagonists. L364,718 (3-100 nM), proglumide (1-10 mM), and the proglumide derivative CR1409 (1-30 microM) each caused a progressive rightward shift in the CCK-8 dose-response curve without a change in maximal amylase secretion. Plotting the data according to the method of Schild indicated competitive inhibition. The Kis for L364,718, CR1409, and proglumide were 0.25 nM, 0.15 microM, and 0.5 mM, respectively. Thus L364,718 was 600-fold more potent than CR1409 and 2,000,000-fold more potent than proglumide in inhibiting CCK-8-induced amylase release. Inhibition of 125I-Bolton-Hunter-CCK-8 binding to acini by these receptor antagonists had a similar rank potency. L364,718 was tested against other pancreatic exocrine secretagogues and was effective against agonists that only act through the CCK receptor. In rats, diversion of pancreatic juice from the duodenum stimulated pancreatic amylase output and elevated plasma CCK levels. The stimulated amylase secretion was blocked by intravenous administration of L364,718. Furthermore, extracted plasma CCK from rats with diversion of pancreatic juice from the duodenum stimulated amylase release from pancreatic acini, and this stimulation was blocked by addition of L364,718.(ABSTRACT TRUNCATED AT 250 WORDS)

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