Congo red modulates ACh-induced Ca²⁺ oscillations in single pancreatic acinar cells of mice

Aim: Congo red, a secondary diazo dye, is usually used as an indicator for the presence of amyloid fibrils. Recent studies show that congo red exerts neuroprotective effects in a variety of models of neurodegenerative diseases. However, its pharmacological profile remains unknown. In this study, we investigated the effects of congo red on ACh-induced Ca²⁺ oscillations in mouse pancreatic acinar cells in vitro. Methods: Acutely dissociated pancreatic acinar cells of mice were prepared. A U-tube drug application system was used to deliver drugs into the bath. Intracellular Ca²⁺ oscillations were monitored by whole-cell recording of Ca²⁺ -activated Cl^- currents and by using confocal Ca²⁺ imaging. For intracellular drug application, the drug was added in pipette solution and diffused into cell after the whole-cell configuration was established. Results: Bath application of ACh (10 nmol/L) induced typical Ca²⁺ oscillations in dissociated pancreatic acinar cells. Addition of congo red (1, 10, 100 μmol/L) dose-dependently enhanced Ach-induced Ca²⁺ oscillations, but congo red alone did not induce any detectable response. Furthermore, this enhancement depended on the concentrations of ACh: congo red markedly enhanced the Ca²⁺ oscillations induced by ACh (10-30 nmol/L), but did not alter the Ca²⁺ oscillations induced by ACh (100-10000 nmol/L). Congo red also enhanced the Ca²⁺ oscillations induced by bath application of IP₃ (30 μmol/L). Intracellular application of congo red failed to alter ACh-induced Ca²⁺ oscillations. Conclusion: Congo red significantly modulates intracellular Ca²⁺ signaling in pancreatic acinar cells, and this pharmacological effect should be fully considered when developing congo red as a novel therapeutic drug.