Abstract
FK506 (tacrolimus)-binding protein (FKBP) is associated with intracellular Ca 2+ release channel and modulates its function. To elucidate the effect of FK506 on Ca 2+ dynamics and Ca 2+-mediated Cl − secretion in airway epithelium, we studied intracellular Ca 2+ ([Ca 2+] i) concentration and Cl −-dependent short-circuit current ( I sc), in cultured bovine tracheal epithelial cells. Addition of ATP induced an increase in [Ca 2+] i, and this response was dose dependently inhibited by FK506. Rapamycin, which binds FKBP with high affinity, likewise inhibited the [Ca 2+] i rise, but cyclosporin A, a specific calcineurin inhibitor, did not. In Cl − secretion studies using Ussing chamber, ATP increased Ca 2+-mediated I sc in amiloride-treated cells, an effect that was inhibited by FK506 and rapamycin but not by cyclosporin A. Therefore, FK506 inhibits Ca 2+ mobilization in airway epithelium via FKBP but not calcineurin-dependent mechanism, which may result in the suppression of Ca 2+-activated Cl − secretion.
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