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 Ca(2+) signals in a complex manner. 2-APB inhibits or potentiates intracellular Ca(2+) signals in different cell types, perhaps through different mechanisms. Here, we report a novel mechanism underlying 2-APB-induced inhibition of agonist-activated Ca(2+) oscillations in mouse pancreatic acinar cells, using patch-clamp and biochemical techniques. Pre-treatment of the cells with 100 microM 2-APB completely abolished ACh- but not inositol trisphosphate (InsP(3))-induced Ca(2+) oscillations, suggesting that the mechanism of inhibition occurs between cytoplasmic receptors and InsP(3) receptor activation. In addition, 100 microM 2-APB significantly inhibited ACh-induced phospholipase C (PLC) activation. These findings indicate that, in mouse pancreatic acinar cells, in addition to modulating InsP(3) receptors and blocking the store-operated Ca(2+) pathway, high concentrations of 2-APB also inhibit agonist-induced Ca(2+) signals by reducing InsP(3) formation.