Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathologic activation of proteases within the pancreatic acinar cell is a key initiating event in acute pancreatitis. Past studies have suggested that the generation of a low-pH environment is critical to this process. Vacuolar adenosine triphosphatase (vATPase) is a multiprotein complex that transports protons across cellular membranes. Activation of the vATPase requires assembly of the soluble (V(1)) subunits on the membrane subunits (V(0)). It is found that conditions that cause protease activation in the acinar cell also cause assembly of V(1) on V(0). Further, inhibitors of vATPase block this protease activation. Ethanol and butanol sensitize the acinar cell to cholecystokinin-induced zymogen activation; vATPase inhibitors also blocked this activation. Activation of the vATPase may be central to the pathologic activation of proteases in the acinar cell and may also modulate the sensitizing effects of alcohols.
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PMID:Vacuolar adenosine triphosphatase and pancreatic acinar cell function. 1695 63

Alcohol consumption has long been associated with cell damage, and it is thought that it is involved in approximately 40% of cases of acute pancreatitis. In the present study, we have investigated the early effects of acute ethanol exposure on cholecystokinin octapeptide (CCK-8)-evoked calcium (Ca2+) signals in mouse pancreatic acinar cells. Cells were loaded with fura-2 and the changes in fluorescence were monitorized using a spectrofluorimeter. Our results show that stimulation of cells with 1 nM CCK-8 led to a transient increase in [Ca2+]c, which consisted of an initial increase followed by a decrease of [Ca2+]c toward a value close to the prestimulation level. In the presence of 50mM ethanol, CCK-8 lead to a greater Ca2+ mobilization compared to that obtained with CCK-8 alone. The peak of CCK-8-evoked Ca2+ response, the "steady-state level" reached 5 min after stimulation, the rate of decay of [Ca2+]c toward basal values and the total Ca2+ mobilization were significantly affected by ethanol pretreatment. Thapsigargin (Tps) induced an increase in [Ca2+]c due to its release from intracellular stores. After stimulation of cells with CCK-8 or Tps in the presence of 50mM ethanol, a greater [Ca2+]c peak response, a slower rate of decay of [Ca2+]c, and higher values of [Ca2+]c were observed. The effects of ethanol might result from a delayed or reduced Ca2+ extrusion from the cytosol toward the extracellular space by plasma membrane Ca2+ adenosine triphosphatase (ATPase), or into the cytosolic stores by the sarcoendoplasmic reticulum Ca2+-ATPase. Participation of mitochondria in Ca2+ handling is also demonstrated. The actions of ethanol on CCK-8 stimulation of cells create a situation potentially leading to Ca2+ overload, which is a common pathological precursor that mediates pancreatitis.
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PMID:Ethanol impairs calcium homeostasis following CCK-8 stimulation in mouse pancreatic acinar cells. 1877 72