Article Figures & Data
Figures
- Fig. 1.
(A) Structure of EPAC (molecular weight = 437 g/mol). (B) Tryptophan metabolism pathway. Indoleamine 2,3-dioxygenase (IDO) is the first and rate-limiting catabolic enzyme in the degradation of the essential amino acid tryptophan along the kynurenine and serotonin pathways. The kynurenine pathway accounts for approximately 95% and the serotonin pathway accounts for 5% of tryptophan catabolism. In addition to IDO, tryptophan 2,3-dioxygenase (TDO) is also responsible for the conversion from tryptophan to kynurenine. IDO1 is expressed throughout the body and is overexpressed in multiple tumor types. IDO2 is similar to IDO1 by 41% at the amino acid level. However, its role in cancer is unclear. TDO is predominantly expressed in the liver and is responsible for the homeostasis of tryptophan levels in the body (Yue et al., 2017).
- Fig. 2.
Serotonin, tryptophan, and kynurenine concentrations in rats following microdialysis studies. (A) Serotonin concentration vs. mid-time points following treatment with various test compounds. Data are presented as concentrations of serotonin at various sample-collecting time points vs. mid-time points. The results are expressed as the mean ± S.E.M. for three to four rats. (B) The area under the curve (AUC) for the concentration of serotonin following the treatment with vehicle, EPAC alone, EPAC plus linezolid, fluoxetine alone, or fluoxetine plus linezolid. The mean serotonin concentration-time data shown in (A) were used to determine the AUC values by standard noncompartmental methods using Phoenix WinNonlin (version 6.4.0; Pharsight Corporation, Mountain View, CA). (C) Tryptophan concentrations vs. mid-time points following treatment with vehicle, EPAC alone, EPAC plus linezolid, fluoxetine alone, or fluoxetine plus linezolid. Data are presented as concentrations of tryptophan at various sample-collecting time points vs. mid-time points. The results are expressed as mean ± S.E.M. for three to four rats.
Tables
- TABLE 1
Brain, CSF, and plasma concentrations of EPAC in rats following intravenous infusion for 4 h (N = 4)
Concentration at 4 h Brain/Plasma Plasma CSF Brain µM µM µM % 0.851 ± 0.18 BQL 0.127 ± 0.039 15 ± 6 BQL, below quantifiable limitation of 0.004 µM.
