Role of calcium homeostasis in gastric mucosal injury and protection.
Using a human gastric mucosal cell line, known as AGS cells, we determined the role that perturbations in intracellular Ca2+ concentration [Ca2+]i might play in cellular injury induced by various damaging agents. For deoxycholate (CD) and ethanol (EtOH) induced damage, a concentration related increase in [Ca2+]i was noted that preceded and closely paralleled the magnitude of injury. Thus, the higher the concentration of DC or EtOH, the more profound were the changes in [Ca2+]i and the resultant degree of cellular injury. Pretreatment with a low concentration of DC (50 microM; called a mild irritant) that was not damaging by itself attenuated injury induced by a damaging concentration (i.e. 250 microM) of DC, and appeared to elicit this protective action through mechanisms that resisted intracellular Ca2+ accumulation. Additional studies indicated that the mechanism of aspirin damage may be similar and that other protective agents such as prostaglandins and growth factors appear to mediate their protective properties through prevention of intracellular Ca2+ alterations. We propose that agents that prevent mucosal injury mediate this activity through a cellular response (involving active Ca2+ efflux) that subsequently provides a protective action by limiting the magnitude of intracellular Ca2+ accumulation.
Miller
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TA
Department of Surgery, Medical College of Virginia Campus at Virginia, Commonwealth University, Richmond 23298, USA.
Kokoska
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ER
Smith
G S
GS
Banan
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A
D001241:Aspirin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology*; D003840:Deoxycholic Acid / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000009:adverse effects; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D013997:Time Factors
D003840:Deoxycholic Acid; D000431:Ethanol; D015544:Inositol 1,4,5-Trisphosphate; D001241:Aspirin; D002118:Calcium