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Stimulatory effects of bilirubin on amylase release from isolated rat pancreatic acini
- Source :
- American Journal of Physiology-Gastrointestinal and Liver Physiology. 282:G249-G256
- Publication Year :
- 2002
- Publisher :
- American Physiological Society, 2002.
-
Abstract
- 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 PLA2partly mediate this process.
- Subjects :
- Male
medicine.medical_specialty
Physiology
Bilirubin
8-Bromo Cyclic Adenosine Monophosphate
In Vitro Techniques
Phospholipases A
chemistry.chemical_compound
Phospholipase A2
Acinus
Physiology (medical)
Internal medicine
medicine
Animals
Amylase
Enzyme Inhibitors
Rats, Wistar
Pancreas
Calcimycin
Protein Kinase C
chemistry.chemical_classification
Ionophores
Hepatology
biology
Gastroenterology
Protein-Tyrosine Kinases
medicine.disease
Rats
Endocrinology
Enzyme
medicine.anatomical_structure
chemistry
Type C Phospholipases
Amylases
Pancreatic juice
biology.protein
Acute pancreatitis
Calcium
Intracellular
Signal Transduction
Vasoactive Intestinal Peptide
Subjects
Details
- ISSN :
- 15221547 and 01931857
- Volume :
- 282
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Accession number :
- edsair.doi.dedup.....e56851a78634651c36bcf7f98a519b0b