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Ethanol exerts dual effects on calcium homeostasis in CCK-8-stimulated mouse pancreatic acinar cells
BACKGROUND: A significant percentage of patients with pancreatitis often presents a history of excessive alcohol consumption. Nevertheless, the patho-physiological effect of ethanol on pancreatitis remains poorly understood. In the present study, we have investigated the early effects of acute ethan...
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777139/ https://www.ncbi.nlm.nih.gov/pubmed/19878551 http://dx.doi.org/10.1186/1471-2121-10-77 |
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author | Fernández-Sánchez, Marcela del Castillo-Vaquero, Angel Salido, Ginés M González, Antonio |
author_facet | Fernández-Sánchez, Marcela del Castillo-Vaquero, Angel Salido, Ginés M González, Antonio |
author_sort | Fernández-Sánchez, Marcela |
collection | PubMed |
description | BACKGROUND: A significant percentage of patients with pancreatitis often presents a history of excessive alcohol consumption. Nevertheless, the patho-physiological effect of ethanol on pancreatitis remains poorly understood. In the present study, we have investigated the early effects of acute ethanol exposure on CCK-8-evoked Ca(2+ )signals in mouse pancreatic acinar cells. Changes in [Ca(2+)](i )and ROS production were analyzed employing fluorescence techniques after loading cells with fura-2 or CM-H(2)DCFDA, respectively. RESULTS: Ethanol, in the concentration range from 1 to 50 mM, evoked an oscillatory pattern in [Ca(2+)](i). In addition, ethanol evoked reactive oxygen species generation (ROS) production. Stimulation of cells with 1 nM or 20 pM CCK-8, respectively led to a transient change and oscillations in [Ca(2+)](i). In the presence of ethanol a transformation of 20 pM CCK-8-evoked physiological oscillations into a single transient increase in [Ca(2+)](i )in the majority of cells was observed. Whereas, in response to 1 nM CCK-8, the total Ca(2+ )mobilization was significantly increased by ethanol pre-treatment. Preincubation of cells with 1 mM 4-MP, an inhibitor of alcohol dehydrogenase, or 10 μM of the antioxidant cinnamtannin B-1, reverted the effect of ethanol on total Ca(2+ )mobilization evoked by 1 nM CCK-8. Cinnamtannin B-1 blocked ethanol-evoked ROS production. CONCLUSION: ethanol may lead, either directly or through ROS generation, to an over stimulation of pancreatic acinar cells in response to CCK-8, resulting in a higher Ca(2+ )mobilization compared to normal conditions. The actions of ethanol on CCK-8-stimulation of cells create a situation potentially leading to Ca(2+ )overload, which is a common pathological precursor that mediates pancreatitis. |
format | Text |
id | pubmed-2777139 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-27771392009-11-15 Ethanol exerts dual effects on calcium homeostasis in CCK-8-stimulated mouse pancreatic acinar cells Fernández-Sánchez, Marcela del Castillo-Vaquero, Angel Salido, Ginés M González, Antonio BMC Cell Biol Research Article BACKGROUND: A significant percentage of patients with pancreatitis often presents a history of excessive alcohol consumption. Nevertheless, the patho-physiological effect of ethanol on pancreatitis remains poorly understood. In the present study, we have investigated the early effects of acute ethanol exposure on CCK-8-evoked Ca(2+ )signals in mouse pancreatic acinar cells. Changes in [Ca(2+)](i )and ROS production were analyzed employing fluorescence techniques after loading cells with fura-2 or CM-H(2)DCFDA, respectively. RESULTS: Ethanol, in the concentration range from 1 to 50 mM, evoked an oscillatory pattern in [Ca(2+)](i). In addition, ethanol evoked reactive oxygen species generation (ROS) production. Stimulation of cells with 1 nM or 20 pM CCK-8, respectively led to a transient change and oscillations in [Ca(2+)](i). In the presence of ethanol a transformation of 20 pM CCK-8-evoked physiological oscillations into a single transient increase in [Ca(2+)](i )in the majority of cells was observed. Whereas, in response to 1 nM CCK-8, the total Ca(2+ )mobilization was significantly increased by ethanol pre-treatment. Preincubation of cells with 1 mM 4-MP, an inhibitor of alcohol dehydrogenase, or 10 μM of the antioxidant cinnamtannin B-1, reverted the effect of ethanol on total Ca(2+ )mobilization evoked by 1 nM CCK-8. Cinnamtannin B-1 blocked ethanol-evoked ROS production. CONCLUSION: ethanol may lead, either directly or through ROS generation, to an over stimulation of pancreatic acinar cells in response to CCK-8, resulting in a higher Ca(2+ )mobilization compared to normal conditions. The actions of ethanol on CCK-8-stimulation of cells create a situation potentially leading to Ca(2+ )overload, which is a common pathological precursor that mediates pancreatitis. BioMed Central 2009-10-30 /pmc/articles/PMC2777139/ /pubmed/19878551 http://dx.doi.org/10.1186/1471-2121-10-77 Text en Copyright © 2009 Fernández-Sánchez et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Fernández-Sánchez, Marcela del Castillo-Vaquero, Angel Salido, Ginés M González, Antonio Ethanol exerts dual effects on calcium homeostasis in CCK-8-stimulated mouse pancreatic acinar cells |
title | Ethanol exerts dual effects on calcium homeostasis in CCK-8-stimulated mouse pancreatic acinar cells |
title_full | Ethanol exerts dual effects on calcium homeostasis in CCK-8-stimulated mouse pancreatic acinar cells |
title_fullStr | Ethanol exerts dual effects on calcium homeostasis in CCK-8-stimulated mouse pancreatic acinar cells |
title_full_unstemmed | Ethanol exerts dual effects on calcium homeostasis in CCK-8-stimulated mouse pancreatic acinar cells |
title_short | Ethanol exerts dual effects on calcium homeostasis in CCK-8-stimulated mouse pancreatic acinar cells |
title_sort | ethanol exerts dual effects on calcium homeostasis in cck-8-stimulated mouse pancreatic acinar cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777139/ https://www.ncbi.nlm.nih.gov/pubmed/19878551 http://dx.doi.org/10.1186/1471-2121-10-77 |
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