Dibutyltin Dichloride Modifies Amylase Release from Isolated Rat Pancreatic Acini

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 [125I]CCK-8 to isolated rat pancreatic acini. Conversely, DBTC potentiated secretin-stimulated amylase release, although it slightly inhibited [125I]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.

[1]  G. Sparmann,et al.  The Course of Pancreatic Fibrosis Induced by Dibutyltin Dichloride (DBTC) , 1999, Annals of the New York Academy of Sciences.

[2]  H. Ohnishi,et al.  Involvement of Rab4 in regulated exocytosis of rat pancreatic acini. , 1999, Gastroenterology.

[3]  I. Shibuya,et al.  Stimulatory effects of vanadate on amylase release from isolated rat pancreatic acini. , 1998, Biochemical pharmacology.

[4]  H. Nizze,et al.  The influence of ethanol on long-term effects of dibutyltin dichloride (DBTC) in pancreas and liver of rats , 1998, Human & experimental toxicology.

[5]  H. Nizze,et al.  Acute Interstitial Pancreatitis in Rats Induced by Dibutyltin Dichloride (DBTC): Pathogenesis and Natural Course of Lesions , 1997, Pancreas.

[6]  M. Löhr,et al.  Pancreatic fibrosis in experimental pancreatitis induced by dibutyltin dichloride. , 1997, Gastroenterology.

[7]  M. Kasuga,et al.  Potentiating effect of insulin on exocrine secretory function in isolated rat pancreatic acini. , 1994, Gastroenterology.

[8]  M. Andreae,et al.  Methyl- and butyltin compounds in water and sediments of the Rhine River , 1991 .

[9]  L. Jonas,et al.  Morphological lesions of pancreas and bile ducts in rats induced by dibutyltin dichloride. , 1991, Archives of toxicology. Supplement. = Archiv fur Toxikologie. Supplement.

[10]  I. Boyer,et al.  Toxicity of dibutyltin, tributyltin and other organotin compounds to humans and to experimental animals. , 1989, Toxicology.

[11]  G. Hennighausen,et al.  Acute pancreatitis and bile duct lesions in rat induced by dibutyltin dichloride. , 1989, Experimental pathology.

[12]  W. Seinen,et al.  Biological activity of organotin compounds--an overview. , 1987, Environmental research.

[13]  J. Short,et al.  Accumulation of Butyltins in Muscle Tissue of Chinook Salmon Reared in Sea Pens Treated With Tri-n-Butyltin , 1986, OCEANS '86.

[14]  T. Kimura,et al.  Ca2+-, phorbol ester-, and cAMP-stimulated enzyme secretion from permeabilized rat pancreatic acini. , 1986, The American journal of physiology.

[15]  W. Seinen,et al.  Triorganotin-induced cytotoxicity to rat thymus, bone marrow and red blood cells as determined by several in vitro assays. , 1986, Toxicology.

[16]  J. Singh.  Phorbol ester (TPA) potentiates noradrenaline and acetylcholine‐evoked amylase secretion in the rat pancreas , 1985, FEBS letters.

[17]  J. De Pont,et al.  Synergistic effect of A23187 and a phorbol ester on amylase secretion from rabbit pancreatic acini , 1984, FEBS letters.

[18]  D. B. Burnham,et al.  Stimulus-secretion coupling in pancreatic acinar cells. , 1984 .

[19]  D. Evans,et al.  Accumulation of bis (tributyltin) oxide by the mud crab, Rhithropanopeus harrisii , 1984 .

[20]  J. E. Thain,et al.  Shell thickening in Crassostrea gigas: Organotin antifouling or sediment induced? , 1983 .

[21]  M. Otsuki,et al.  Effect of diabetes mellitus on the regulation of enzyme secretion by isolated rat pancreatic acini. , 1982, The Journal of clinical investigation.

[22]  P. Lange,et al.  The relationship between the length of the alkyl chain of dialkyltin compounds and their effects on thymus and bile ducts in mice. , 1980, Archives of toxicology. Supplement. = Archiv fur Toxikologie. Supplement.

[23]  M. M. Bradford.  A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[24]  M. Ceska,et al.  A new and rapid method for the clinical determination of alpha-amylase activities in human serum and urine. Optimal conditions. , 1969, Clinica chimica acta; international journal of clinical chemistry.

[25]  P. Magee,et al.  The biliary and hepatic lesion produced experimentally by dibutyltin salts. , 1958, The Journal of pathology and bacteriology.

[26]  F. Wróblewski,et al.  Lactic Dehydrogenase Activity in Blood.∗ , 1955, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.