Hepatic Bile Acid Reuptake in the Rat Depends on Bile Acid Conjugation but Not on Agonistic Properties towards FXR and TGR5
Abstract
:1. Introduction
2. Results
2.1. Total, Total Conjugated, and Total Unconjugated BA Concentrations in the Portal Vein and Vena Cava
2.2. Concentrations of Primary BAs in the Portal Vein and Vena Cava
2.3. Concentrations of Secondary BAs in the Portal Vein and Vena Cava
2.4. Concentrations of Murine Specific BAs in the Portal Vein and Vena Cava
2.5. Concentration of FXR and TGR5 Agonistic BAs in Peripheral Blood is below Activating Concentrations, and Hepatic Extraction of BAs is Independent of Their Potency and Efficacy towards These Receptors
3. Discussion
4. Materials and Methods
4.1. Animal Studies
4.1.1. Ethical Considerations
4.1.2. In Vivo Study
4.2. Biochemical Measurements
4.3. Data Analysis and Statistics
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are not available from the authors. |
Plasma from Vena Portae | Plasma from Vena Cava Inferior | ||||||
---|---|---|---|---|---|---|---|
Bile acid | Baseline (µM) | 40 min (µM) | AUC (µM x min) | Baseline (µM) | 40 min (µM) | AUC (µM x min) | Ratio: V. Cava/V. Portae |
Collected | |||||||
Total | 58.9 ± 10.7 | 87.4 ± 25.1 | 2650 ± 634 | 18.3 ± 5.18 | 28.0 ± 8.68 | 726 ± 231 ** | 0.25 ± 0.07 (0 min) 0.20 ± 0.03 (40 min) |
Total conjugated | 22.5 ± 9.32 | 30.4 ± 10.1 | 899 ± 317 | 1.43 ± 0.57 | 2.18 ± 0.91 | 92.4 ± 45.1 * | 0.08 ± 0.03 (0 min) 0.07 ± 0.02 (40 min) |
Total unconjugated | 36.4 ± 12.1 | 63.7 ± 19.8 | 1752 ± 535 | 16.8 ± 7.30 | 19.1 ± 6.56 | 636 ± 222 ** | 0.35 ± 0.05 (0 min) 0.29 ± 0.02 (40 min) |
Primary BAs | |||||||
CA | 13.6 ± 4.10 | 21.9 ± 5.87 | 190 ± 50.4 | 4.67 ± 1.73 | 5.54 ± 1.35 | 658 ± 168 ** | 0.30 ± 0.03 (0 min) 0.28 ± 0.02 (40 min) |
TCA | 10.5 ± 4.39 | 12.6 ± 4.38 | 404 ± 153 | 0.56 ± 0.19 | 0.81 ± 0.32 | 37.4 ± 17.2 * | 0.08 ± 0.03 (0 min) 0.07 ± 0.02 (40 min) |
CDCA | 4.41 ± 2.67 | 6.50 ± 3.21 | 186 ± 99.4 | 2.89 ± 1.18 | 2.34 ± 1.01 | 93.3 ± 50.2 | 0.61 ± 0.06 (0 min) 0.43 ± 0.03 (40 min) |
TCDCA | 2.30 ± 0.91 | 3.34 ± 0.96 | 95.1 ± 25.8 | 0.31 ± 0.08 | 0.37 ± 0.09 | 16.0 ± 5.31 ** | 0.19 ± 0.03 (0 min) 0.13 ± 0.01 (40 min) |
Secondary BAs | |||||||
DCA | 2.45 ± 0.85 | 4.87 ± 1.66 | 128 ± 43.4 | 0.97 ± 0.35 | 1.14 ± 0.35 | 43.2 ± 12.9 * | 0.43 ± 0.03 (0 min) 0.33 ± 0.08 (40 min) |
TDCA | 0.92 ± 0.18 | 1.34 ± 0.39 | 39.4 ± 10.5 | 0.18 ± 0.17 | 0.20 ± 0.035 | 8.86 ± 1.20 | 0.25 ± 0.04 (0 min) 0.19 ± 0.03 (40 min) |
UDCA | 7.02 ± 3.28 | 15.7 ± 7.60 | 387 ± 179 | 5.44 ± 2.89 | 6.43 ± 3.285 | 197 ± 91.3 * | 0.25 ± 0.04 (0 min) 0.19 ± 0.03 (40 min) |
TUDCA | 1.58 ± 0.81 | 3.69 ± 1.80 | 387 ± 179 | 0.26 ± 0.07 | 0.40 ± 0.19 | 197 ± 91.3 | 0.47 ± 0.13 (0 min) 0.39 ± 0.13 (40 min) |
Murine specific BAs | |||||||
MCA alpha | 1.95 ± 0.87 | 4.23 ± 1.77 | 97.4 ± 39.4 | 0.93 ± 0.44 | 1.00 ± 0.42 | 34.8 ± 13.6 * | 0.46 ± 0.04 (0 min) 0.37 ± 0.06 (40 min) |
MCA beta | 2.65 ± 0.94 | 6.42 ± 2.02 | 144 ± 46.3 | 1.26 ± 0.49 | 1.85 ± 0.58 | 60.0 ± 15.9 * | 0.42 ± 0.04 (0 min) 0.69 ± 0.37 (40 min) |
TMCA alpha | 2.01 ± 0.82 | 2.98 ± 0.91 | 81.9 ± 25.7 | 0.29 ± 0.08 | 0.36 ± 0.10 | 14.9 ± 5.09 | 0.25 ± 0.05 (0 min) 0.16 ± 0.03 (40 min) |
TMCA beta | 5.29 ± 2.60 | 6.52 ± 2.22 | 203 ± 78.1 | 0.25 ± 0.07 | 0.39 ± 0.14 | 20.7 ± 10.9 ** | 0.16 ± 0.06 (0 min) 0.08 ± 0.01 (40 min) |
TGR5/FXR | |||||||
Agonists | 2.52 ± 0.74 | 3.75 ± 0.97 | 112 ± 28.3 | 1.09 ± 0.48 | 1.27 ± 0.33 | 40.4 ± 13.7 ** | 0.38 ± 0.04 (0 min) 0.25 ± 0.03 (40 min) |
Non-agonists | 8.73 ± 1.64 | 12.7 ± 2.85 | 382 ± 78.6 | 2.74 ± 0.91 | 4.03 ± 1.06 | 110 ± 29.4 *** | 0.25 ± 0.03 (0 min) 0.31 ± 0.05 (40 min) |
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Trammell, S.A.J.; Svenningsen, J.S.; Holst, J.J.; Gillum, M.P.; Kuhre, R.E. Hepatic Bile Acid Reuptake in the Rat Depends on Bile Acid Conjugation but Not on Agonistic Properties towards FXR and TGR5. Molecules 2020, 25, 2371. https://doi.org/10.3390/molecules25102371
Trammell SAJ, Svenningsen JS, Holst JJ, Gillum MP, Kuhre RE. Hepatic Bile Acid Reuptake in the Rat Depends on Bile Acid Conjugation but Not on Agonistic Properties towards FXR and TGR5. Molecules. 2020; 25(10):2371. https://doi.org/10.3390/molecules25102371
Chicago/Turabian StyleTrammell, Samuel A. J., Jens S. Svenningsen, Jens J. Holst, Matthew P. Gillum, and Rune E. Kuhre. 2020. "Hepatic Bile Acid Reuptake in the Rat Depends on Bile Acid Conjugation but Not on Agonistic Properties towards FXR and TGR5" Molecules 25, no. 10: 2371. https://doi.org/10.3390/molecules25102371