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 μM for 24 h. The value of 50% inhibitory concentration, IC 50 , of tetrahydropapaveroline was 7.5 μM. 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 μM). In addition, tetrahydropapaveroline inhibited the activity of TPH, prepared from the P815 cells (P815-TPH), with the IC 50 value of 8.4 μM. 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 μM. These data indicate that tetrahydropapaveroline leads to a decrease in serotonin content by inhibiting TPH activity in P815 cells.