Activation of alpha1A-adrenoceptors by genistein at concentrations lower than that to inhibit tyrosine kinase in cultured C2C12 cells.
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 alpha (1)-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 alpha (1)-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 alpha (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 alpha (1A)-AR at a concentration (1 micromol/L) lower than that (50 micromol/L) needed to abolish the insulin-stimulated phosphorylation of PTK. The obtained data indicate an activation of alpha (1A)-AR by genistein to increase the glucose uptake into C2C12 cells and this supports the application of genistein as a TK inhibitor.
Jou
Shuo-Bin
SB
Department of Neurology, School of Medicine and Hospital, China Medical University, Taichung City, Taiwan, R.O.C.
Huang
Ching-Chiu
CC
Liu
I-Min
IM
Cheng
Juei-Tang
JT
D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D002478:Cells, Cultured / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019833:Genistein / Q000008:administration & dosage / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology; D018517:Plant Roots; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D029908:Pueraria; D011869:Radioligand Assay; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D010936:Plant Extracts; D018340:Receptors, Adrenergic, alpha-1; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D005947:Glucose