Activation of α_1A-Adrenoceptors by Genistein at Concentrations Lower than that to Inhibit Tyrosine Kinase in Cultured C₂C₁₂ Cells

Abstract

Genistein, an isoflavonoid natural product, is widely used to inhibit protein tyrosine kinase (PTK). In the present study, we investigated the possible influence of genistein on α₁-adrenoceptors (AR) in cultured C₂C₁₂ cells. Genistein enhanced the uptake of radioactive glucose into C₂C₁₂ cells in a concentration-dependent manner. Similar results were also observed in samples treated with daidzein, the inactive congener for PTK inhibition. The effect of genistein on α₁-AR was further characterized using the displacement of [³ H]prazosin binding in C₂C₁₂ cells. The increase in radioactive glucose uptake by genistein was abolished by RS17053 at a concentration sufficient to block α_1A-AR. The pharmacological inhibition of phospholipase C (PLC) by U73122 resulted in a concentration-dependent reduction of genistein-stimulated glucose uptake in C₂C₁₂ cells. This inhibition by U73122 was specific because the inactive congener, U73343, failed to modify the action of genistein. Moreover, genistein can activate α_1A-AR at a concentration (1 μmol/L) lower than that (50 μmol/L) needed to abolish the insulin-stimulated phosphorylation of PTK. The obtained data indicate an activation of α_1A-AR by genistein to increase the glucose uptake into C₂C₁₂ cells and this supports the application of genistein as a TK inhibitor.

Key words

Genistein - C₂C₁₂ cells - α_1A-adrenoceptor - phospholipase C - protein tyrosine kinase

References

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