Inhibitory effects of tetrahydropapaverine on serotonin biosynthesis in murine mastocytoma P815 cells.
The inhibitory effects of tetrahydropapaverine on serotonin biosynthesis in serotonin-producing murine mastocytoma P815 cells were investigated. Tetrahydropapaverine at concentration ranges of 5-20 microM decreased serotonin content in a concentration-dependent manner in P815 cells and showed 42.1% inhibition of serotonin content at 5.0 microM at 24 hr. The value of 50% inhibitory concentration, IC50, of tetrahydropapaverine was 6.2 microM. Under these conditions, tryptophan hydroxylase (EC 1.14.16.4, TPH) was inhibited for 24-36 hr after treatment with tetrahydropapaverine in P815 cells (49.1% inhibition at 7.5 microM). However, aromatic L-amino acid decarboxylase activity was not affected by tetrahydropapaverine. In addition, tetrahydropapaverine inhibited the activity of TPH, prepared from the P815 cells (P815-TPH), with the IC50 value of 5.7 microM. Tetrahydropapaverine un-competitively inhibited P815-TPH with the substrate L-tryptophan, and non-competitively with the cofactor DL-6-methyl-5,6,7,8-tetrahydropteridin. The Ki value of tetrahydropapaverine with L-tryptophan was 10.1 microM. These data indicate that tetrahydropapaverine leads to a decrease in serotonin content by the inhibition of TPH activity in P815 cells.
Kim
Eung Il
EI
College of Pharmacy, Chungbuk National University, San 48, Gaeshin-Dong, Heungduk-Gu, Cheongju 361-763, Republic of Korea.
Kang
Min Hee
MH
Lee
Myung Koo
MK
D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D005453:Fluorescence; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D012701:Serotonin / Q000096:biosynthesis*; D013997:Time Factors; D014364:Tryptophan / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
D007546:Isoquinolines; C063395:tetrahydropapaverine; D012701:Serotonin; D014364:Tryptophan; D014365:Tryptophan Hydroxylase; D001142:Aromatic-L-Amino-Acid Decarboxylases