Inhibitory effects of tetrahydropapaverine on serotonin biosynthesis in murine mastocytoma P815 cells

Life Sci. 2004 Sep 3;75(16):1949-57. doi: 10.1016/j.lfs.2004.04.017.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aromatic-L-Amino-Acid Decarboxylases / metabolism
  • Fluorescence
  • Isoquinolines / chemistry
  • Isoquinolines / pharmacology*
  • Mice
  • Serotonin / biosynthesis*
  • Time Factors
  • Tryptophan / metabolism
  • Tryptophan Hydroxylase / antagonists & inhibitors*
  • Tumor Cells, Cultured

Substances

  • Isoquinolines
  • tetrahydropapaverine
  • Serotonin
  • Tryptophan
  • Tryptophan Hydroxylase
  • Aromatic-L-Amino-Acid Decarboxylases