Reduction of serotonin content by tetrahydropapaveroline in murine mastocytoma P815 cells.
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.
Kim
Eung Il
EI
College of Pharmacy, and Research Center for Bioresource and Health, Chungbuk National University, San 48, Gaeshin-Dong, Heungduk-Gu, Cheongju 361-763, South Korea.
Yin
Shouyu
S
Kang
Min Hee
MH
Hong
Jin Tae
JT
Oh
Ki Wan
KW
Lee
Myung Koo
MK
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
D012702:Serotonin Antagonists; D012701:Serotonin; D013765:Tetrahydropapaveroline; D014365:Tryptophan Hydroxylase