Stimulatory effects of bilirubin on amylase release from isolated rat pancreatic acini

2002 ◽  
Vol 282 (2) ◽  
pp. G249-G256 ◽  
Author(s):  
Yoshihide Hirohata ◽  
Masatoshi Fujii ◽  
Yoshinori Okabayashi ◽  
Yoshikuni Nagashio ◽  
Mitsuo Tashiro ◽  
...  
Keyword(s):  
Etiologic Factor ◽  
Dependent Manner ◽  
Camp Content ◽  
Amylase Release ◽  
Pancreatic Acini ◽  
Kinase C ◽  
A 23187 ◽  
Intracellular Ca ◽  
Pancreatic Exocrine ◽  
Isolated Rat

Considered to be an etiologic factor of acute pancreatitis, hypersecretion of pancreatic juice and digestive enzymes is often associated with hyperbilirubinemia. We explored the intracellular mechanisms through which bilirubin affects pancreatic exocrine secretory function by examining the effect of bilirubin on isolated rat pancreatic acini. Bilirubin stimulated amylase release in a concentration- and time-dependent manner, significantly increasing amylase release at concentrations >5 mg/100 ml and after 15 min of incubation. Coincubation of bilirubin with vasoactive intestinal polypeptide, 8-bromo-cAMP, or A-23187 had a synergistic effect on amylase release, whereas coincubation with CCK-8, carbamylcholine, or 12- O-tetradecanoylphorbol 13-acetate had an additive effect. Bilirubin did not affect acinar cAMP content or Ca2+efflux. Intracellular Ca2+ pool depletion had no influence on bilirubin-evoked amylase release. The protein kinase C (PKC) inhibitors staurosporine and calphostin C partially but significantly inhibited bilirubin-stimulated amylase release, whereas the PKA inhibitor H-89 did not. The tyrosine kinase (TK) inhibitor genistein, phospholipase A2 (PLA2) inhibitor indoxam, and PLC inhibitor U-73122 also inhibited amylase release. Bilirubin significantly translocated PKC activity from the cytosol to the membrane fraction and activated TK in cytosol and membrane fractions. These results indicate that bilirubin stimulates amylase release by activating PKC and TK in rat pancreatic acini and that PLC and PLA2 partly mediate this process.

Potentiation of carbachol-induced amylase release by propionate in guinea pig and vole pancreatic acini

1999 ◽  
Vol 277 (3) ◽  
pp. R767-R775
Author(s):  
Etsumori Harada ◽  
Megumi Mitani ◽  
Takashi Takeuchi
Keyword(s):  
Guinea Pig ◽  
Secretory Pathway ◽  
Direct Action ◽  
Camp Level ◽  
Amylase Secretion ◽  
Ionophore A23187 ◽  
Camp Content ◽  
Amylase Release ◽  
Pancreatic Acini ◽  
Intracellular Ca

The action of propionate, one of the major end products of microbial fermentation in herbivores was investigated in isolated, perifused pancreatic acini of guinea pigs, voles, and mice. With the use of guinea pig acini, 100 μM propionate had no effect, whereas 300 and 600 μM increased amylase release by six- and ninefold, respectively. Simultaneous perifusion of carbachol (CCh) 10 μM plus propionate 100 μM in guinea pig acini produced a potentiated secretory response that was 130% higher than the summated value obtained with CCh and propionate alone. The potentiation by propionate (100 μM) of CCh (10 μM)-induced amylase release was also obtained in vole pancreatic acini, but the mouse pancreatic preparation did not exhibit a similar potentiation. In contrast to CCh, propionate (100–600 μM) alone had no significant effect on intracellular Ca2+ concentration ([Ca2+]i) and did not alter [Ca2+]ielicited by CCh. Ca ionophore A23187 (5 μM)-induced amylase release in guinea pig acini was enhanced twofold by the addition of propionate. Cellular cAMP content was increased slightly by propionate, but did not alter dose dependently. The cAMP level with combinations of CCh and propionate was almost same as that with CCh alone and propionate alone. Staurosporine did not modify amylase secretion induced by a combination of CCh and propionate. These results suggest that propionate, in addition to a direct action on amylase release, potentiates CCh-induced amylase release in guinea pig and vole acini via a secretory pathway not associated with an increase in [Ca2+]iand cellular cAMP.

Cyclosporine A Inhibits Protein-Kinase-C-Mediated Amylase Release from Isolated Rat Pancreatic Acini

Digestion ◽  
1994 ◽  
Vol 55 (6) ◽  
pp. 380-388 ◽  
Author(s):  
Michael Höcker ◽  
Ingo H. Waschulewski ◽  
Horst F. Kern ◽  
Klaus A. Domagk ◽  
Rainer Schwarzhoff ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cyclosporine A ◽  
Amylase Release ◽  
Pancreatic Acini ◽  
Kinase C ◽  
Isolated Rat

Glutathione Might Exert an Important Function in Caerulein-Stimulated Amylase Release in Isolated Rat Pancreatic Acini

Pancreas ◽  
2002 ◽  
Vol 24 (1) ◽  
pp. 53-62 ◽  
Author(s):  
Honggang Yu ◽  
Hanne Klonowski-Stumpe ◽  
Reinhard Lüthen
Keyword(s):  
Amylase Release ◽  
Pancreatic Acini ◽  
Isolated Rat

PGE2 triggers recovery of transmucosal resistance via EP receptor cross talk in porcine ischemia-injured ileum

2001 ◽  
Vol 281 (2) ◽  
pp. G375-G381 ◽  
Author(s):  
Anthony T. Blikslager ◽  
Susan M. Pell ◽  
Karen M. Young
Keyword(s):  
Cross Talk ◽  
Splice Variants ◽  
Camp Content ◽  
Ep Receptors ◽  
Ussing Chambers ◽  
A 23187 ◽  
Receptor Interactions ◽  
Intracellular Ca ◽  
Ep Receptor ◽  
Receptor Cross Talk

16,16-Dimethyl-PGE2 (PGE2) may interact with one of four prostaglandin type E (EP) receptors, which signal via cAMP (via EP2 or EP4 receptors) or intracellular Ca2+ (via EP1 receptors). Furthermore, EP3 receptors have several splice variants, which may signal via cAMP or intracellular Ca2+. We sought to determine the PGE2 receptor interactions that mediate recovery of transmucosal resistance ( R) in ischemia-injured porcine ileum. Porcine ileum was subjected to 45 min of ischemia, after which the mucosa was mounted in Ussing chambers. Tissues were pretreated with indomethacin (5 μM). Treatment with the EP1, EP2, EP3, and EP4 agonist PGE2 (1 μM) elevated R twofold and significantly increased tissue cAMP content, whereas the EP2 and EP4 agonist deoxy-PGE1 (1 μM) or the EP1 and EP3 agonist sulprostone (1 μM) had no effect. However, a combination of deoxy-PGE1 and sulprostone stimulated synergistic elevations in R and tissue cAMP content. Furthermore, treatment of tissues with deoxy-PGE1 and the Ca2+ ionophore A-23187 stimulated synergistic increases in R and cAMP, indicating that PGE2 triggers recovery of R via EP receptor cross talk mechanisms involving cAMP and intracellular Ca2+.

Low [Mg2+]o induces contraction and [Ca2+]i rises in cerebral arteries: roles of Ca2+, PKC, and PI3

2000 ◽  
Vol 279 (6) ◽  
pp. H2898-H2907 ◽  
Author(s):  
Zhi-Wei Yang ◽  
Jun Wang ◽  
Tao Zheng ◽  
Bella T. Altura ◽  
Burton M. Altura
Keyword(s):  
Cerebral Arteries ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Voltage Gated ◽  
Selective Antagonist ◽  
Kinase C ◽  
Pkc Isoforms ◽  
Intracellular Ca ◽  
Basilar Arteries ◽  
Specific Antagonist

Removal of extracellular Ca2+ concentration ([Ca2+]o) and pretreatment of canine basilar arterial rings with either an antagonist of voltage-gated Ca2+ channels (verapamil), a selective antagonist of the sarcoplasmic reticulum Ca2+ pump [thapsigargin (TSG)], caffeine plus a specific antagonist of ryanodine-sensitive Ca2+ release (ryanodine), or ad- myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]- mediated Ca2+ release antagonist (heparin) markedly attenuates low extracellular Mg2+ concentration ([Mg2+]o)-induced contractions. Low [Mg2+]o-induced contractions are significantly inhibited by pretreatment of the vessels with Gö-6976 [a protein kinase C-α (PKC-α)- and PKC-βI-selective antagonist], bisindolylmaleimide I (Bis, a specific antagonist of PKC), and wortmannin or LY-294002 [selective antagonists of phosphatidylinositol-3 kinases (PI3Ks)]. These antagonists were also found to relax arterial contractions induced by low [Mg2+]o in a concentration-dependent manner. The absence of [Ca2+]o and preincubation of the cells with verapamil, TSG, heparin, or caffeine plus ryanodine markedly attenuates the transient and sustained elevations in the intracellular Ca2+ concentration ([Ca2+]i) induced by low-[Mg2+]o medium. Low [Mg2+]o-produced increases in [Ca2+]i are also suppressed markedly in the presence of Gö-6976, Bis, wortmannin, or LY-294002. The present study suggests that both Ca2+ influx through voltage-gated Ca2+ channels and Ca2+ release from intracellular stores [both Ins(1,4,5)P3sensitive and ryanodine sensitive] play important roles in low-[Mg2+]o medium-induced contractions of isolated canine basilar arteries. Such contractions are clearly associated with activation of PKC isoforms and PI3Ks.

Ca2+-, phorbol ester-, and cAMP-stimulated enzyme secretion from permeabilized rat pancreatic acini

1986 ◽  
Vol 250 (5) ◽  
pp. G698-G708 ◽  
Author(s):  
T. Kimura ◽  
K. Imamura ◽  
L. Eckhardt ◽  
I. Schulz
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Protein Release ◽  
Enzyme Secretion ◽  
Dependent Manner ◽  
Intact Cells ◽  
Pancreatic Acini ◽  
Kinase C ◽  
Kinase A

Enzyme secretion from the exocrine pancreas is stimulated by receptor-activated breakdown of phosphatidylinositol 4,5-bisphosphate and consequent rise of both inositol 1,4,5-trisphosphate (IP3) and diacylglycerol, which leads to Ca2+ release and to activation of protein kinase C, respectively. Another way involves receptor-mediated stimulation of adenylate cyclase and consequent rise of cAMP and activation of protein kinase A. In the present work we have studied direct stimulation, inhibition, and mutual interaction of these pathways on enzyme secretion from isolated rat pancreatic acini that had been permeabilized by treatment with saponin or digitonin. The data were compared with those obtained in isolated intact acini. The data show that with increasing free Ca2+ concentrations greater than 10(-6) M protein release increases in "leaky" but not in "intact" cells and is maximal at approximately 10(-3) M, increasing about twofold compared with that in the absence of Ca2+. In the presence of the acetylcholine analogue carbachol, this effect of Ca2+ is enhanced by about threefold in leaky cells and is also present in intact cells to a similar extent. cAMP and its analogues, dibutyryl cAMP (dbcAMP) and 8-bromo-cAMP stimulate protein release by about twofold in the presence of Ca2+ in leaky cells. In intact acini cAMP has no effect, and cAMP analogues stimulate enzyme secretion by about twofold in some but not all experiments. Similarly, forskolin, an activator of adenylate cyclases and inhibitors of cyclic nucleotide-dependent phosphodiesterases, such as 3-isobutyl-1-methylxanthine (IBMX) and R0 201724, stimulate protein release in permeabilized acini. The Ca2+-binding protein calmodulin has no effect on enzyme secretion, whereas the calmodulin antagonist trifluoperazine dihydrochloride stimulates protein release in leaky but not in intact acini. The activator of protein kinase C, 12-O-tetradecanoylphorbol 13-acetate (TPA) stimulates protein release in a Ca2+-dependent manner and enhances cAMP-induced secretion. The effects of carbachol, TPA, cAMP, and a combination of both TPA and cAMP are inhibited by the polyamine spermine in permeabilized cells. Spermine has no effect on carbachol-induced enzyme secretion in intact cells. The data suggest that enzyme secretion from pancreatic acinar cells is mediated by cAMP protein kinase A and by Ca2+ phospholipid protein kinase C in a Ca2+-dependent way and that interaction occurs between both pathways.

Chronic oral administration of synthetic trypsin inhibitor camostate reduces amylase release from isolated rat pancreatic acini

1995 ◽  
Vol 18 (2) ◽  
pp. 135-143
Author(s):  
Makoto Otsuki ◽  
Masatoshi Fujii ◽  
Takahiko Nakamura ◽  
Satoshi Tani ◽  
Yshinori Okabayashi
Keyword(s):  
Oral Administration ◽  
Trypsin Inhibitor ◽  
Amylase Release ◽  
Pancreatic Acini ◽  
Isolated Rat

Actions of Neuromedin-B and Neuromedin-C on Amylase Release from Isolated Rat Pancreatic Acini

Pancreas ◽  
1987 ◽  
Vol 2 (3) ◽  
pp. 252-257 ◽  
Author(s):  
Makoto Otsuki ◽  
Masatoshi Fuji ◽  
Takahiko Nakamura ◽  
Satoshi Tani ◽  
Toru Oka ◽  
...  
Keyword(s):  
Amylase Release ◽  
Pancreatic Acini ◽  
Neuromedin B ◽  
Isolated Rat

CCK activates p90rsk in rat pancreatic acini through protein kinase C

1997 ◽  
Vol 272 (3) ◽  
pp. G401-G407 ◽  
Author(s):  
M. J. Bragado ◽  
A. Dabrowski ◽  
G. E. Groblewski ◽  
J. A. Williams
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Kinase Inhibitor ◽  
Threshold Concentration ◽  
Mitogen Activated Protein Kinase ◽  
Maximal Effect ◽  
Dependent Manner ◽  
Pancreatic Acini ◽  
Kinase C ◽  
Mitogen Activated Protein

The presence of the 90-kDa ribosomal S6 protein kinase (p90(rsk)) in isolated rat pancreatic acini was demonstrated by Western blotting and immunoprecipitation with anti-p90(rsk). Cholecystokinin (CCK) activated p90(rsk) activity in a time- and dose-dependent manner and increased its phosphorylation. The threshold concentration of CCK was 10 pM and the maximal effect was seen at 1 nM. An increase in p90(rsk) was observed 1 min after 1 nM CCK stimulation, reaching a maximum at 10 min, when p90(rsk) activity was increased 5.4-fold. Carbachol and bombesin, but not vasoactive intestinal peptide, also activated p90(rsk). CCK-induced activation of p90(rsk) appears to be mediated by protein kinase C (PKC), since 12-O-tetradecanoylphorbol-13-acetate increased p90(rsk) activity 5.3-fold. GF-109293X, a potent inhibitor of PKC, strongly inhibited CCK-evoked p90(rsk) activity. Treatment of acini with ionomycin or 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid had no effect, indicating that mobilization of intracellular Ca2+ by CCK is not important in p90(rsk) activation. Although there were some quantitative differences in the extent of inhibition, the specific inhibitors [rapamycin, wortmannin, mitogen-activated protein kinase (MAPK) kinase inhibitor PD98059, and GF-109293X] had parallel effects on p90(rsk) and p42(mapk) activities, consistent with a model in which p90(rsk) can be regulated in acini by MAPK.

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