2-Aminoethoxydiphenyl borate inhibits agonist-induced Ca²⁺ signals by blocking inositol trisphosphate formation in acutely dissociated mouse pancreatic acinar cells

Evidence suggests that 2-aminoethoxydiphenyl borate (2-APB) modulates intracellular Ca²⁺ signals in a complex manner. 2-APB inhibits or potentiates intracellular Ca²⁺ signals in different cell types, perhaps through different mechanisms. Here, we report a novel mechanism underlying 2-APB-induced inhibition of agonist-activated Ca²⁺ oscillations in mouse pancreatic acinar cells, using patch-clamp and biochemical techniques. Pre-treatment of the cells with 100 μM 2-APB completely abolished ACh-but not inositol trisphosphate (InsP₃)-induced Ca ²⁺ oscillations, suggesting that the mechanism of inhibition occurs between cytoplasmic receptors and InsP₃ receptor activation. In addition, 100 μM 2-APB significantly inhibited ACh-induced phospholipase C (PLC) activation. These findings indicate that, in mouse pancreatic acinar cells, in addition to modulating InsP₃ receptors and blocking the store-operated Ca²⁺ pathway, high concentrations of 2-APB also inhibit agonist-induced Ca²⁺ signals by reducing InsP₃ formation.