Phenylarsine oxide evokes intracellular calcium increases and amylase secretion in isolated rat pancreatic acinar cells.
The effects of the thiol reagent, phenylarsine oxide (PAO, 10(-5)-10(-3) M ), a membrane-permeable trivalent arsenical compound that specifically complexes vicinal sulfhydryl groups of proteins to form stable ring structures, were studied by monitoring intracellular free calcium concentration ([Ca2+]i) and amylase secretion in collagenase dispersed rat pancreatic acinar cells. PAO increased [Ca2+]i by mobilizing calcium from intracellular stores, since this increase was observed in the absence of extracellular calcium. PAO also prevented the CCK-8-induced signal of [Ca2+]i and inhibited the oscillatory pattern initiated by aluminium fluoride (AlF-4). In addition to the effects of PAO on calcium mobilization, it caused a significant increase in amylase secretion and reduced the secretory response to either CCK-8 or AlF-4. The effects of PAO on both [Ca2+]i and amylase release were reversed by the sulfhydryl reducing agent, dithiothreitol (2 mM). Pretreatment of acinar cells with high concentration of ryanodine (50 microM) reduced the PAO-evoked calcium release. However, PAO was still able to release a small fraction of Ca2+ from acinar cells in which agonist-releasable Ca2+ pools had been previously depleted by thapsigargin (0.5 microM) and ryanodine receptors were blocked by 50 microM ryanodine. We conclude that, in pancreatic acinar cells, PAO mainly releases Ca2+ from the ryanodine-sensitive calcium pool and consequently induces amylase secretion. These effects are likely to be due to the oxidizing effects of this compound.
Lajas
A I
AI
Department of Physiology, Faculty of Veterinary Science, University of Extremadura, Cáceres, Spain.
Pozo
M J
MJ
Camello
P J
PJ
Salido
G M
GM
Pariente
J A
JA
D000681:Amylases / Q000378:metabolism*; D000818:Animals; D001152:Arsenicals / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012844:Sincalide / Q000494:pharmacology
D001152:Arsenicals; D004791:Enzyme Inhibitors; C029341:oxophenylarsine; D000681:Amylases; D012844:Sincalide; D002118:Calcium