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 (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.
Lyu
R M
RM
Department of Pharmacology, School of Medicine, University of Alabama at Birmingham 35294.
Smith
J B
JB
D001920:Bradykinin / Q000037:antagonists & inhibitors*; D002104:Cadmium / Q000037:antagonists & inhibitors*; D002118:Calcium / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D019833:Genistein; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D010738:Type C Phospholipases / Q000378:metabolism
D007527:Isoenzymes; D007529:Isoflavones; D010982:Platelet-Derived Growth Factor; D002104:Cadmium; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D010738:Type C Phospholipases; D001920:Bradykinin; D002118:Calcium