title: Activation of alpha1A-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 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.
authors.affiliation: Department of Neurology, School of Medicine and Hospital, China Medical University, Taichung City, Taiwan, R.O.C.
authors.forename: Shuo-Bin
authors.initials: SB
authors.lastname: Jou
authors.forename: Ching-Chiu
authors.initials: CC
authors.lastname: Huang
authors.forename: I-Min
authors.initials: IM
authors.lastname: Liu
authors.forename: Juei-Tang
authors.initials: JT
authors.lastname: Cheng
mesh_terms: 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
chemical_list: D000317:Adrenergic alpha-Antagonists; D010936:Plant Extracts; D018340:Receptors, Adrenergic, alpha-1; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D005947:Glucose