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Dibutyltin dichloride modifies amylase release from isolated rat pancreatic acini
Yoshikuni Nagashio1, Yoshihide Hirohata, Toshiharu Akiyama
1Third Department of Internal Medicine, University of Occupational and Environmental Health-Japan, School of Medicine, Kitakyushu, Japan.
Introduction:
Dibutyltin dichloride (DBTC) is widely used as a stabilizer for polyvinylchloride plastics and is of particular toxicologic interest.
Aim:
To examine the effects of DBTC on pancreatic exocrine function in isolated rat pancreatic acini.
Methodology:
Isolated rat pancreatic acini were incubated with various secretagogues in the presence or absence of DBTC. We investigated the effects of DBTC on amylase release, receptor binding, and protein kinase C (PKC) enzyme activity.
Results:
DBTC reduced cholecystokinin octapeptide (CCK-8)-stimulated and carbamylcholine-stimulated amylase release and the binding of [(125)I]CCK-8 to isolated rat pancreatic acini. Conversely, DBTC potentiated secretin-stimulated amylase release, although it slightly inhibited [(125)I]secretin binding to its receptors. In addition, DBTC potentiated amylase release stimulated by vasoactive intestinal peptide, 8-bromoadenosine 3', 5'-monophosphate (8Br-cAMP) or calcium ionophore A23187, whereas it had no influence on amylase release stimulated by 12-O-tetradecanoylphorbol 13-acetate. The protein kinase C (PKC) inhibitor calphostin C abolished the DBTC-induced potentiation of amylase release stimulated by 8Br-cAMP or A23187. Moreover, DBTC caused a significant translocation of PKC enzyme activity from cytosol to membrane fraction.
Conclusions:
These results indicate that DBTC reduces CCK-8- and carbamylcholine-stimulated amylase release by inhibiting their receptor bindings to pancreatic acini, whereas it potentiates cAMP-mediated amylase release by activating PKC in isolated rat pancreatic acini.