thapsigargin and tenidap

The anti-inflammatory agent tenidap has previously been shown to inhibit antigen-induced secretion in tumor mast cells. We have investigated the possibility that this effect is due to modulation of the Ca2+ response in mast cells and in particular that tenidap might be an inhibitor of the Ca2+ influx pathway or channel in these and other non-excitable cells. Tenidap inhibited the antigen-induced increase in intracellular Ca2+ measured both in cell suspensions and at the single cell level using digital imaging of Fura-2 fluorescence. Tenidap also inhibited both antigen- and thapsigargin-induced 45Ca influx across the plasma membrane at concentrations similar to those required for the inhibition of secretion. Somewhat unexpectedly, the compound itself caused some release of calcium from intracellular stores; however, this effect did not appear to be related to the inhibition of calcium influx or secretion. In mouse pituitary tumour (AtT-20) cells, tenidap inhibited depolarization-induced increases in intracellular Ca2+ suggesting that this compound also inhibits Ca2+ influx through voltage-sensitive calcium channels. We conclude that tenidap has a number of interesting effects on calcium handling which makes it a potentially valuable tool for the study of calcium movements particularly in non-excitable cells.

Topics: Animals; Antigens; Calcium; Calcium Channels; Indoles; Inositol Phosphates; Leukemia, Basophilic, Acute; Mast Cells; Mice; Oxindoles; Phosphatidylinositols; Pituitary Neoplasms; Rats; Signal Transduction; Terpenes; Thapsigargin; Tumor Cells, Cultured