title: Reduction of serotonin content by tetrahydropapaveroline in murine mastocytoma P815 cells.
abstract: The inhibitory effects of tetrahydropapaveroline on serotonin biosynthesis in serotonin-producing murine mastocytoma P815 cells were investigated. Tetrahydropapaveroline decreased serotonin content in a concentration-dependent manner in P815 cells and showed 44.9% reduction of serotonin content at a concentration of 5.0 microM for 24 h. The value of 50% inhibitory concentration, IC(50), of tetrahydropapaveroline was 7.5 microM. Under these conditions, tryptophan hydroxylase (EC 1.14.16.4, TPH) was inhibited for 24-36 h after treatment with tetrahydropapaveroline in P815 cells (46.6% inhibition at 7.5 microM). In addition, tetrahydropapaveroline inhibited the activity of TPH, prepared from the P815 cells (P815-TPH), with the IC(50) value of 8.4 microM. Inhibition of P815-TPH by tetrahydropapaveroline was found to be non-competitive both with the substrate L-tryptophan and with the cofactor DL-6-methyl-5,6,7,8-tetrahydropterine. The K(i) value of tetrahydropapaveroline with L-tryptophan was 9.29 microM. These data indicate that tetrahydropapaveroline leads to a decrease in serotonin content by inhibiting TPH activity in P815 cells.
authors.affiliation: College of Pharmacy, and Research Center for Bioresource and Health, Chungbuk National University, San 48, Gaeshin-Dong, Heungduk-Gu, Cheongju 361-763, South Korea.
authors.forename: Eung Il
authors.initials: EI
authors.lastname: Kim
authors.forename: Shouyu
authors.initials: S
authors.lastname: Yin
authors.forename: Min Hee
authors.initials: MH
authors.lastname: Kang
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
authors.forename: Ki Wan
authors.initials: KW
authors.lastname: Oh
authors.forename: Myung Koo
authors.initials: MK
authors.lastname: Lee
mesh_terms: D000818:Animals; D007700:Kinetics; D034801:Mastocytoma; D051379:Mice; D012701:Serotonin / Q000096:biosynthesis*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013765:Tetrahydropapaveroline / Q000494:pharmacology*; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D012702:Serotonin Antagonists; D012701:Serotonin; D013765:Tetrahydropapaveroline; D014365:Tryptophan Hydroxylase