The melatonin receptor antagonist luzindole induces Ca2+ mobilization, reactive oxygen species generation and impairs trypsin secretion in mouse pancreatic acinar cells

Biochimica Et Biophysica Acta. General Subjects
Matias EstarasAntonio Gonzalez

Abstract

In this work we studied the effects of the melatonin receptor-antagonist luzindole (1 μM-50 μM) on isolated mouse pancreatic acinar cells. Changes in intracellular free-Ca2+ concentration, reactive oxygen species production and trypsin secretion were analyzed. Luzindole induced increases in [Ca2+]i that diminished CCK-8 induced Ca2+ mobilization, compared with that observed when CCK-8 was applied alone. Treatment of cells with thapsigargin (1 μM), in the absence of Ca2+ in the extracellular medium, evoked a transient increase in [Ca2+]i. The additional incubation of cells with luzindole (10 μM) failed to induce further mobilization of Ca2+. In the presence of luzindole a concentration-dependent increase in ROS generation was observed that decreased in the absence of Ca2+ or by pretreatment of cells with melatonin (100 μM). Incubation of pancreatic acinar cells with luzindole (10 μM) impaired CCK-8-induced trypsin secretion. Melatonin was unable to revert the effect of luzindole on CCK-8-induced trypsin secretion. The melatonin receptor-inhibitor luzindole induces Ca2+-mediated pro-oxidative conditions and impairment of enzyme secretion, which creates a situation in pancreatic acinar cells that might compromise their function. T...Continue Reading

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Citations

Jul 8, 2020·Biology of the Cell·Matias EstarasAntonio Gonzalez
Aug 2, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Matias EstarasAntonio Gonzalez

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