Unconjugated Bile Acids and Alcohols Inhibit Degranulation of Stimulated RBL-2H3 Cells

These findings demonstrate that bile acids and alcohols inhibit SOC-mediated Ca²⁺ entry by directly interacting with Orai1, thereby blocking mast cell degranulation. Although the concentrations required for this effect were near cytotoxic levels owing to detergent-like properties, the results uncovered a novel molecular interaction between steroid structures and Orai1. This mechanistic insight provides a foundation for the development of targeted small molecule modulators of Orai1-mediated calcium entry, offering potential therapeutic strategies for allergic and inflammatory disorders.