title: Stimulatory effects of the soy phytoestrogen genistein on noradrenaline transporter and serotonin transporter activity.
abstract: We examined the effects of genistein, one of the major soy phytoestrogens, on the activity of noradrenaline transporter (NAT) and serotonin transporter. Treatment with genistein (10 nM-10 microM) for 20 min stimulated [(3)H]noradrenaline (NA) uptake by SK-N-SH cells. Genistein also stimulated [(3)H]NA uptake and [(3)H]serotonin uptake by NAT and serotonin transporter transiently transfected COS-7 cells, respectively. Kinetics analysis of the effect of genistein on NAT activity in NAT-transfected COS-7 cells revealed that genistein significantly increased the maximal velocity of NA transport with little or no change in the affinity. Scatchard analysis of [(3)H]nisoxetine binding to NAT-transfected COS-7 cells showed that genistein increased the maximal binding without altering the dissociation constant. Although genistein is also known to be an inhibitor of tyrosine kinases, daidzein, another soy phytoestrogen and an inactive genistein analogue against tyrosine kinases, had little effect on [(3)H]NA uptake by SK-N-SH cells. The stimulatory effects on NAT activity were observed by treatment of tyrphostin 25, an inhibitor of epidermal growth factor receptor tyrosine kinase, whereas orthovanadate, a protein tyrosine phosphatase inhibitor, suppressed [(3)H]NA uptake by NAT-transfected COS-7 cells. These findings suggest that genistein up-regulates the activity of neuronal monoamine transporters probably through processes involving protein tyrosine phosphorylation.
authors.affiliation: Department of Pharmacology, School of Medicine, University of Occupational and Environmental Health, Yahatanishiku, Kitakyushu, Japan. toyohira@med.uoeh-u.ac.jp
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Toyohira
authors.forename: Susumu
authors.initials: S
authors.lastname: Ueno
authors.forename: Masato
authors.initials: M
authors.lastname: Tsutsui
authors.forename: Hideaki
authors.initials: H
authors.lastname: Itoh
authors.forename: Norio
authors.initials: N
authors.lastname: Sakai
authors.forename: Naoaki
authors.initials: N
authors.lastname: Saito
authors.forename: Kojiro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yanagihara
mesh_terms: D000818:Animals; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005473:Fluoxetine / Q000031:analogs & derivatives / Q000378:metabolism; D000077267:Fulvestrant; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D009447:Neuroblastoma; D009638:Norepinephrine / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D048789:Phytoestrogens / Q000494:pharmacology*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D013025:Glycine max / Q000737:chemistry*; D014162:Transfection; D014316:Tritium; D014638:Vanadates / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D050484:Norepinephrine Plasma Membrane Transport Proteins; D048789:Phytoestrogens; D011960:Receptors, Estrogen; D050486:Serotonin Plasma Membrane Transport Proteins; D005473:Fluoxetine; D014316:Tritium; C011386:nisoxetine; D000077267:Fulvestrant; D012701:Serotonin; D014638:Vanadates; D004958:Estradiol; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases; D009638:Norepinephrine