Ca2+-mobilizing action of the microsomal Ca2+-ATPase inhibitor thapsigargin.

Ca2+ mobilization evoked by the activation of drug receptors is due to Ca2+ entry from the extracellular medium into cells as well as Ca2+ release from intracellular stores. However, the intracellular Ca2+ stores are diverse and the mechanism of Ca2+ entry is unknown. Thapsigargin （TG）, a sesquiterpene lactone extracted from the root of the umbelliferous plant Thapsia garganica, is a non-phorbol ester type tumor promoter. Since it has been found that TG has a specific inhibitory action on microsomal Ca2+ -ATPase, TG is widely used for the analysis of the nature of intracellular Ca2+ stores and the mechanism of Ca2+ mobilization. This article reviews the recent studies on Ca2+ mobilization of TG in several kinds of cells. TG mobilizes Ca2+ from extracellular medium as well as from intracellular stores in many types of cells. Based on the action of TG on intracellular Ca2+ stores, it was found that the intracellular Ca2+ store in parotid acinar cells has at least two compartments, and that an agonist- and inositol trisphosphate-sensitive Ca2+ pool in pancreatoma AR4-2J cells exits in or closely associated with the nuclear envelope. Ca2+ entry induced by TG is called capacitative Ca2+ entry, by which depletion of Ca2+ in the intracellular store activates Ca2+ entry. In this review TG, as an excellent tool for the study of Ca2+ mobilization and cellular function compared to other Ca2+ -ATPase inhibitors, is also discussed.departmental bulletin pape