Inhibitory effects of tetrahydropapaverine on serotonin biosynthesis in murine mastocytoma P815 cells.
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| Abstract |
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.
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| Authors | Eung Il Kim, Min Hee Kang, Myung Koo Lee |
| Journal | Life sciences (Life Sci) Vol. 75 Issue 16 Pg. 1949-57 (Sep 03 2004) ISSN: 0024-3205 [Print] Netherlands |
| PMID | 15306162 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't) |
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