Effect of dephostatin on intracellular free calcium concentration and amylase secretion in isolated rat pancreatic acinar cells.
This study investigates the effects of dephostatin, a new tyrosine phosphatase inhibitor, on intracellular free calcium concentration ([Ca2+]i) and amylase secretion in collagenase dispersed rat pancreatic acinar cells. Dephostatin evoked a sustained elevation in [Ca2+]i by mobilizing calcium from intracellular calcium stores in either the absence of extracellular calcium or the presence of lanthanium chloride (LaCl3). Pretreatment of acinar cells with dephostatin prevented cholecystokinin-octapeptide (CCK-8)-induced signal of [Ca2+]i and inhibited the oscillatory pattern initiated by aluminium fluoride (AlF4), whereas co-incubation with CCK-8 enhances the plateau phase of calcium response to CCK-8 without modifying the transient calcium spike. The effects of dephostatin on calcium mobilization were reversed by the presence of the sulfhydryl reducing agent, dithiothreitol. Stimulation of acinar cells with thapsigargin in the absence of extracellular Ca2+ resulted in a transient rise in [Ca2+]i. Application of dephostatin in the continuous presence of thapsigargin caused a small but sustained elevation in [Ca2+]i. These results suggest that dephostatin can mobilize Ca2+ from both a thapsigargin-sensitive and thapsigargin-insensitive intracellular stores in pancreatic acinar cells. In addition, dephostatin can stimulate the release of amylase from pancreatic acinar cells and moreover, reduce the secretory response to CCK-8. The results indicate that dephostatin can release calcium from intracellular calcium pools and consequently induces amylase secretion in pancreatic acinar cells. These effects are likely due to the oxidizing effects of this compound.
Lajas
A I
AI
Department of Physiology, Faculty of Veterinary Sciences, University of Extremadura, Cáceres, Spain.
Pozo
M J
MJ
Camello
P J
PJ
Salido
G M
GM
Singh
J
J
Pariente
J A
JA
D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000494:pharmacology; D000681:Amylases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019833:Genistein / Q000494:pharmacology; D006873:Hydroquinones / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012844:Sincalide / Q000494:pharmacology; D012969:Sodium Fluoride / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors
D017607:Aluminum Compounds; D002712:Chlorides; D004791:Enzyme Inhibitors; D006873:Hydroquinones; C084037:dephostatin; D000077410:Aluminum Chloride; D019284:Thapsigargin; D012969:Sodium Fluoride; D019833:Genistein; D000681:Amylases; D012844:Sincalide; D002118:Calcium