Mechanism of damnacanthal-induced [Ca(2+)](i) elevation in human dermal fibroblasts.
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.
Aoki
K
K
Department of Neurosurgery, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.
Parent
A
A
Zhang
J
J
D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000037:antagonists & inhibitors*; D051381:Rats; D012867:Skin / Q000166:cytology / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology
D000880:Anthraquinones; D004791:Enzyme Inhibitors; C079170:damnacanthal; D019284:Thapsigargin; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D001920:Bradykinin; D002118:Calcium