Genistein inhibits calcium release by platelet-derived growth factor but not bradykinin or cadmium in human fibroblasts |
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Authors: | Rong-Ming Lyu Jeffrey Bingham Smith |
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Institution: | (1) Department of Pharmacology, Schools of Medicine and Dentistry, University of Alabama at Birmingham, 35294 Birmingham, Alabama, USA |
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Abstract: | Cd2+ provokes inositol trisphosphateproduction and releases stored Ca2+, apparently by binding to a zinc site in the external domain of an orphan receptor. One pM Cd2+ evokes an immediate spike in cytosolic free Ca2+, which is similar to that evoked by bradykinin. Platelet-derived growth factor (PDGF) also increases free Ca2+ in human dermalfibroblasts, but there is a distinct lag before free Ca2+ rises in response to PDGF. Genistein, which selectively inhibits tyrosine kinases, markedly inhibited Ca2+ mobilization evoked by PDGF. Calcium mobilization triggered by cadmium or bradykinin was relatively insensitive to genistein. The PDGF receptor is known to be a tyrosine kinase, whichphosphorylates and thereby activatesphospholipase C, whereas a G protein couples the bradykinin receptor to anotherphospholipase C isoform. These findings support the hypothesis that the orphan receptor triggered by cadmium is coupled to phospholipase C via a G protein.Abbreviations BSA
bovine serum albumin
- BK
bradykinin
- Ca2+]i
cytosolic free calcium
- DME
Dulbecco's modified Eagle's medium
- FBS
fetal bovine serum
- HEPES
4-(2-hydroxyethyl)-1-piperazine-ethanesulfonic acid
- IC50
concentration that produces 50% inhibition
- PDGF
platelet-derived growth factor
- PSS
physiological salts solution
- SE
standard error of the mean |
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Keywords: | genistein xenobiotic receptor calcium inositol zinc nickel |
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