Oxidizing effects of vanadate on calcium mobilization and amylase release in rat pancreatic acinar cells.
The effects of vanadate were examined by monitoring intracellular free calcium concentration ([Ca2+]i) and amylase secretion in collagenase-dispersed rat pancreatic acinar cells. Vanadate increased [Ca2+]i by mobilizing calcium from agonist-releasable intracellular calcium stores, since this increase was observed in the absence of extracellular calcium and vanadate failed to increase [Ca2+]i after treatment with thapsigargin in calcium-free medium. Moreover, pretreatment of acinar cells with vanadate prevented the cholecystokinin octapeptide (CCK-8)-induced signal of [Ca2+]i, whereas co-incubation with CCK-8 potentiated the plateau phase of calcium response to CCK-8 without modifying the transient calcium spike. The effects of vanadate on calcium mobilization were reversed by the presence of the sulfhydryl reducing agent dithiothreitol. Vanadate also activated the calcium influx, since an additional enhancement of calcium influx induced by thapsigargin-evoked intracellular store depletion was observed and vanadate reversed the inhibitory effect of lanthanum (an inhibitor of calcium entry) into acinar cells. In addition, vanadate evoked a concentration-dependent release of amylase from pancreatic acinar cells and moreover, reduced the secretory response to CCK-8. We conclude that, in pancreatic acinar cells, vanadate releases calcium from the agonist-releasable intracellular calcium pool and consequently induces amylase secretion. These effects are likely due to the oxidizing effects of this compound.
Pariente
J A
JA
Department of Physiology, Faculty of Veterinary Sciences, University of Extremadura, Cáceres, Spain. pariente@unex.es
Lajas
A I
AI
Pozo
M J
MJ
Camello
P J
PJ
Salido
G M
GM
D000681:Amylases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D010084:Oxidation-Reduction; D010179:Pancreas / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014638:Vanadates / Q000494:pharmacology*
D014638:Vanadates; D000681:Amylases; D002118:Calcium