Effect of cinnamtannin B-1 on cholecystokinin-8-evoked responses in mouse pancreatic acinar cells.
1. Cinnamtannin B-1 is a naturally occurring A-type proanthocyanidin that belongs to a class of polyphenols widely distributed throughout the plant kingdom and exhibiting anti-oxidant properties. 2. In the present study, we examined the effects of cinnamtannin B-1 on cholecystokinin octapeptide (CCK-8)-evoked Ca(2+) mobilization, reactive oxygen species (ROS) production and amylase secretion in the exocrine pancreas. 3. Stimulation of cells with 1 nmol/L CCK-8 led to a transient increase in the cytosolic free calcium concentration ([Ca(2+) ](c) ), followed by a decrease towards a value close to the prestimulation level. In the presence of 10 μmol/L cinnamtannin B-1, stimulation of cells with CCK-8 resulted in a smaller [Ca(2+) ](c) peak response, a faster rate of decay of [Ca(2+) ](c) and lower values for the steady state of [Ca(2+) ](c) , compared with the effect of CCK-8 alone. Cinnamtannin B-1 decreased Ca(2+) influx after depletion of intracellular stores by either CCK-8 or thapsigargin (1 μmol/L). Conversely, CCK-8 increased the fluorescence of 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate acetyl ester (CM-H(2) DCFDA), reflecting an increase in oxidation. Cinnamtannin B-1 reduced CCK-8-induced oxidation of CM-H(2) DCFDA. Cholecystokinin-8 had a biphasic effect on amylase secretion, producing maximum at a concentration of 0.1 nmol/L and reducing secretion at higher concentrations. Pre-incubation of cells with 10 μmol/L cinnamtannin B-1 significantly attenuated the inhibition of enzyme secretion in response to high concentrations of CCK-8 (i.e. >10(-10) mol/L). Finally, the anti-oxidant protected acinar cells against CCK-8-induced cell death. 4. The beneficial effects of cinnamtannin B-1 appear to be mediated by a reduction in intracellular Ca(2+) overload, ROS production and intracellular accumulation of digestive enzymes, which is a common pathological precursor that mediates pancreatitis.
Rivera-Barreno
Ramon
R
Department of Medical Sciences, Institute of Biomedical Sciences, Autonomous University of Juarez, Ciudad Juarez, México.
del Castillo-Vaquero
Angel
A
Salido
Gines M
GM
Gonzalez
Antonio
A
D000681:Amylases / Q000378:metabolism; D000818:Animals; D000872:Anthocyanins / Q000302:isolation & purification / Q000494:pharmacology*; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology*; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002766:Cholecystokinin / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D027442:Laurus; D008297:Male; D051379:Mice; D010179:Pancreas / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D044945:Proanthocyanidins; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism
D000872:Anthocyanins; D000975:Antioxidants; D010446:Peptide Fragments; D044945:Proanthocyanidins; D017382:Reactive Oxygen Species; C410885:cholecystokinin 8; C517872:cinnamtannin B-1; D002766:Cholecystokinin; D000681:Amylases; D002118:Calcium