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.
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism