RX871024 induces Ca²⁺ mobilization from thapsigargin-sensitive stores in mouse pancreatic β-cells

The effects of RX871024, a compound with an imidazoline structure, on cytoplasmic-free Ca²⁺ concentration ([Ca²⁺](i)) in mouse pancreatic β- cells were studied. RX871024 modulates [Ca²⁺](i) by at least two mechanisms. One mechanism involves closure of ATP-regulated K⁺ channels, resulting in membrane depolarization, opening of voltage-gated L-type Ca²⁺ channels, and a subsequent increase in [Ca²⁺](i). Another mechanism, reported here for the first time, deals with RX871024-induced mobilization of Ca²⁺ from nonmitochondrial thapsigargin-sensitive intracellular stores. Reduced glutathione, inhibitors of cytochrome P-450, and monoaminooxidases A and B blocked this Ca²⁺ mobilization. It is concluded that the mechanism of RX871024-induced Ca²⁺ mobilization from intracellular stores involves changes in the oxidation/reduction state of the pancreatic β-cell and may be controlled by cytochrome P-450.