Dibutyltin dichloride modifies amylase release from isolated rat pancreatic acini.
BACKGROUND
Dibutyltin dichloride (DBTC) is widely used as a stabilizer for polyvinylchloride plastics and is of particular toxicologic interest.


OBJECTIVE
To examine the effects of DBTC on pancreatic exocrine function in isolated rat pancreatic acini.


METHODS
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.
Nagashio
Yoshikuni
Y
Third Department of Internal Medicine, University of Occupational and Environmental Health-Japan, School of Medicine, Kitakyushu, Japan.
Hirohata
Yoshihide
Y
Akiyama
Toshiharu
T
Otsuki
Makoto
M
D000681:Amylases / Q000378:metabolism*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004357:Drug Synergism; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D009947:Organotin Compounds / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012633:Secretin / Q000493:pharmacokinetics; D012844:Sincalide / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D018679:Cholinergic Agonists; D007166:Immunosuppressive Agents; D007457:Iodine Radioisotopes; D007476:Ionophores; D009947:Organotin Compounds; D012633:Secretin; D014660:Vasoactive Intestinal Peptide; D000001:Calcimycin; D002217:Carbachol; D011493:Protein Kinase C; D000681:Amylases; C020735:dibutyldichlorotin; D012844:Sincalide