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Effect of cinnamtannin B‐1 on cholecystokinin‐8‐evoked responses in mouse pancreatic acinar cells
Author(s) -
RiveraBarreno Ramon,
CastilloVaquero Angel del,
Salido Gines M,
Gonzalez Antonio
Publication year - 2010
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2010.05424.x
Subject(s) - cholecystokinin , stimulation , chemistry , medicine , endocrinology , thapsigargin , intracellular , secretion , amylase , cytosol , enzyme , biochemistry , biology , receptor
Summary 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.