Caffeine and 2-Aminoethoxydiphenyl Borate (2-APB) Have Different Ability to Inhibit Intracellular Calcium Mobilization in Pancreatic Acinar Cell

Caffeine and 2-Aminoethoxydiphenyl Borate (2-APB) Have Different Ability to Inhibit Intracellular Calcium Mobilization in Pancreatic Acinar Cell

Inositol 1,4,5-trisphosphate receptors (InsP₃Rs) modulate Ca^2＋ release from intracellular Ca^2＋ store and are extensively expressed in the membrane of endoplasmic/sarcoplasmic reticulum and Golgi. Although caffeine and 2-aminoethoxydiphenyl borate (2-APB) have been widely used to block InsP₃Rs, the use of these is limited due to their multiple actions. In the present study, we examined and compared the ability of caffeine and 2-APB as a blocker of Ca^2＋ release from intracellular Ca^2＋ stores and Ca^2＋ entry through store-operated Ca^2＋ (SOC) channel in the mouse pancreatic acinar cell. Caffeine did not block the Ca^2＋ entry, but significantly inhibited carbamylcholine (CCh)-induced Ca^2＋ release. In contrast, 2-APB did not block CCh-induced Ca^2＋ release, but remarkably blocked SOC-mediated Ca^2＋ entry at lower concentrations. In permeabilized acinar cell, caffeine had an inhibitory effect on InsP₃-induced Ca^2＋ release, but 2-APB at lower concentration, which effectively blocked Ca^2＋ entry, had no inhibitory action. At higher concentrations, 2-APB has multiple paradoxical effects including inhibition of InsP₃-induced Ca^2＋ release and direct stimulation of Ca^2＋ release. Based on the results, we concluded that caffeine is useful as an inhibitor of InsP₃R, and 2-APB at lower concentration is considered a blocker of Ca^2＋ entry through SOC channels in the pancreatic acinar cell.