Genistein inhibits calcium release by platelet-derived growth factor but not bradykinin or cadmium in human fibroblasts

Cd2+ provokes inositol trisphosphate production and releases stored Ca2+, apparently by binding to a zinc site in the external domain of an orphan receptor. One microM Cd2+ evokes an immediate spike in cytosolic free Ca2+, which is similar to that evoked by bradykinin. Platelet-derived growth factor...

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Bibliographic Details
Published in:Cell biology and toxicology 1993-04, Vol.9 (2), p.141-148
Main Authors: RONG-MING LYU, SMITH, B
Format: Article
Language:English
Subjects:
Biological and medical sciences
Bradykinin - antagonists & inhibitors
Cadmium - antagonists & inhibitors
Calcium - metabolism
Chemical and industrial products toxicology. Toxic occupational diseases
Fibroblasts - drug effects
Fibroblasts - metabolism
Genistein
Humans
In Vitro Techniques
Isoenzymes - metabolism
Isoflavones - pharmacology
Medical sciences
Metals and various inorganic compounds
Platelet-Derived Growth Factor - antagonists & inhibitors
Protein-Tyrosine Kinases - antagonists & inhibitors
Toxicology
Type C Phospholipases - metabolism
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Summary:Cd2+ provokes inositol trisphosphate production and releases stored Ca2+, apparently by binding to a zinc site in the external domain of an orphan receptor. One microM 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 dermal fibroblasts, 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, which phosphorylates and thereby activates phospholipase C gamma, whereas a G protein couples the bradykinin receptor to another phospholipase C isoform. These findings support the hypothesis that the orphan receptor triggered by cadmium is coupled to phospholipase C via a G protein.
ISSN:0742-2091
1573-6822
DOI:10.1007/BF00757576