Damnacanthal is a potent and selective inhibitor of p56 lck tyrosine kinase in a variety of tissues. We have found, however, using the Ca 2+ microfluorimetry technique, that damnacanthal releases intracellular Ca 2+ stores and promotes Ca 2+ entry in human dermal fibroblasts. The effect of damnacanthal on the peak [Ca 2+] i values and the latent time to the peak was concentration-dependent. Damnacanthal releases Ca 2+ from thapsigargin-sensitive Ca 2+ stores, and the Ca 2+ stores responding to damnacanthal were overlapped with those of bradykinin. Damnacanthal-induced Ca 2+ entry was mediated by voltage-dependent and voltage-independent Ca 2+ channels. This effect of damnacanthal on intracellular Ca 2+ mobilization was also observed in cultured bovine coronary endothelial cells but not demonstrated in freshly isolated rat basilar smooth muscle cells. Our study suggests that damnacanthal increases intracellular Ca 2+ by releasing Ca 2+ from internal stores and promoting Ca 2+ entry. The relationship between the actions of damnacanthal on tyrosine kinase and intracellular Ca 2+ requires further investigation.
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