Cyclopiazonic acid discharges intracellular Ca2+ stores and stimulates Ca2+ influx in cultured human gingival fibroblasts

The effect of cyclopiazonic acid (CPA) on changes in the intracellular free Ca2+ concentration ([Ca2+]i) evoked by bradykinin (BK), histamine (HIST) and thapsigargin (TG) was investigated in human gingival fibroblasts. CPA itself dose-dependently stimulated [Ca2+]i responses in both the absence and presence of extracellular Ca2+. Pretreatment with CPA (< 5 microM) enhanced the [Ca2+]i responses evoked by 5 nM BK and 1 mM HIST. However, CPA-pretreatment depressed the [Ca2+]i response evoked by 1 microM TG in a dose-dependent manner. Moreover, CPA accelerated the Ca2+ influx caused by 5 nM BK and 1mM HIST, but did not alter that caused by 1 microM TG. These results indicate that CPA discharges intracellular Ca2+ stores, resulting in their depletion, and enhances Ca2+ influx across the plasma membrane.