Phenylarsine Oxide Evokes Intracellular Calcium Increases and Amylase Secretion in Isolated Rat Pancreatic Acinar Cells

• Published in: Cellular signalling 1999-10, Vol.11 (10), p.727-734
• Main Authors: Lajas, Ana I, Pozo, Maria J, Camello, Pedro J, Salido, Gines M, Pariente, Jose A
• Format: Article
• Language: English
• Subjects: amylase; Amylases - secretion; Animals; Arsenicals - pharmacology; Calcium; Calcium - metabolism; Cells, Cultured; Enzyme Inhibitors - pharmacology; Intracellular Fluid - metabolism; Male; Pancreas - cytology; Pancreas - metabolism; Pancreas - secretion; Pancreatic acinar cell; phenylarsine oxide; Rats; Rats, Wistar; Sincalide - pharmacology; thapsigargin; Thiol reagent
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/S0898-6568(99)00044-3

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 ([Ca 2+] i) and amylase secretion in collagenase dispersed rat pancreatic acinar cells. PAO increased [Ca 2+] 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 [Ca 2+] 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 [Ca 2+] i and amylase release were reversed by the sulfhydryl reducing agent, dithiothreitol (2 mM). Pretreatment of acinar cells with high concentration of ryanodine (50 μM) reduced the PAO-evoked calcium release. However, PAO was still able to release a small fraction of Ca 2+ from acinar cells in which agonist-releasable Ca 2+ pools had been previously depleted by thapsigargin (0.5 μM) and ryanodine receptors were blocked by 50 μM ryanodine. We conclude that, in pancreatic acinar cells, PAO mainly releases Ca 2+ 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.