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

• 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
• ISSN: 0742-2091; 1573-6822
• DOI: 10.1007/BF00757576

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.