ラット膵腺房細胞のＦＫ５０６誘発性カルシウム放出

抄録

The effect of the immunosuppressant drug FK506 on microsomal Ca²⁺ release was investigated in rat pancreatic acinar cells. When FK506 (0.1-200 μM) was added to pancreatic microsomal vesicles at a steady state of ⁴⁵Ca²⁺ uptake, FK506 caused a dose-dependent and a biphasic release of ⁴⁵Ca²⁺. Almost 10% of total ⁴⁵Ca²⁺ uptake was released at FK506 concentrations up to 10 μM (K_m = 0.5 μM), and 60% of total ⁴⁵Ca²⁺ uptake was released at FK506 concentrations over 10 μM (K_m = 55 μM). The presence of cyclic ADP-ribose (0.5 μM), which is known to modulate the ryanodine receptor (RyR), increased the FK506 (< 10 μM)-induced ⁴⁵Ca²⁺ release. The presence of heparin (200 μg/ml), an inhibitor of the inositol 1,4,5-trisphosphate receptor (IP₃R), resulted in significant inhibition of the FK506 (30 μM)-induced ⁴⁵Ca²⁺ release. These results indicate that two types of FK506-induced Ca²⁺ release mechanisms operate in the endoplasmic reticulum of rat pancreatic acinar cells: a high-affinity mechanism of Ca²⁺ release, which involves activation of the RyR, and a low-affinity mechanism of Ca²⁺ release, which involves activation of the IP₃R. FK506 is known to modulate the RyR or the IP₃R by dissociating FK506-binding protein (FKBP) from the receptor. To determine the involvement of FKBP in the FK506-induced ⁴⁵Ca²⁺ release, the effect of an FKBP antibody on the release was investigated. [J Physiol Sci. 2008;58 Suppl:S200]