A Novel Perspective and Approach to Intestinal Octreotide Absorption: Sinomenine-Mediated Reversible Tight Junction Opening and Its Molecular Mechanism
Abstract
:1. Introduction
2. Results and Discussion
2.1. Everted Gut Sacs Studies in Rats
2.2. Intravenous (i.v.) and Oral Pharmacokinetic Studies in Rats
2.3. The Cytotoxic Effect of SN on Caco-2 Cell Monolayers
2.4. Effect of SN on the TEER and FD-4 Permeability of Caco-2 Cell Monolayers
2.5. Effect of Sinomenine on the Transport of OCT across Caco-2 Cell Monolayers
2.6. Gene and Protein Levels for the Expression of Claudin-1
2.7. Immunofluorescent Staining for Claudin-1
2.8. Mechanism of SN-Mediated Reversible TJ Opening—Shift of PKC-α
2.9. Discussion
3. Experimental Section
3.1. Materials
3.2. Animals Ethics
3.3. Methods
3.3.1. Everted Gut Sacs in Rats
3.3.2. Pharmacokinetics of OCT after i.v. and Oral Administration
3.3.3. Cell Culture
3.3.4. Lactate Dehydrogenase Assay
3.3.5. Transepithelial Electrical Resistance Measurement and FD-4 Permeability
3.3.6. OCT Transport on the Caco-2 Cell Monolayers
3.3.7. Real-Time PCR Analysis
3.3.8. Western Blotting
3.3.9. Immunofluorescent Staining
3.3.10. Statistical Analysis
4. Conclusions
Acknowledgements
Conflict of Interest
References
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Group | Tmax (min) | Cmax (ng/mL) | AUC (ng/mL/min) | F% | ER |
---|---|---|---|---|---|
OCT p.o. | 30 | 44.33 ± 6.66 | 4,023.33 ± 417.14 | 1.63 ± 0.31 | 1 |
OCT + 0.5% SN p.o. | 30 | 255.00 ± 8.72 * | 21,268.33 ± 1,136.48 # | 8.67 ± 1.73 $ | 5.3 |
OCT i.v. | 10 | 307.00 ± 6.00 | 25,135.83 ± 4,548.65 |
TEER reading | 1 | 2 | 3 | 4 | 5 | 7 | TEER (Ω·cm2) |
---|---|---|---|---|---|---|---|
Blankgroup | 104 | 107 | 101 | 105 | 106 | 102 | 104.17 ± 2.32 |
cells | 760 | 710 | 830 | 760 | 772 | 790 | 746.11 ± 46.57 |
Group | Papp (×10−6 cm/s) | R (Papptest/Pappcontrol) |
---|---|---|
Control (10 μM OCT) | 2.67 ± 0.015 | 1 |
0.5% SN + 10 μM OCT | 5.89 ± 0.038 * | 2.2 |
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Li, Y.; Duan, Z.; Tian, Y.; Liu, Z.; Wang, Q. A Novel Perspective and Approach to Intestinal Octreotide Absorption: Sinomenine-Mediated Reversible Tight Junction Opening and Its Molecular Mechanism. Int. J. Mol. Sci. 2013, 14, 12873-12892. https://doi.org/10.3390/ijms140612873
Li Y, Duan Z, Tian Y, Liu Z, Wang Q. A Novel Perspective and Approach to Intestinal Octreotide Absorption: Sinomenine-Mediated Reversible Tight Junction Opening and Its Molecular Mechanism. International Journal of Molecular Sciences. 2013; 14(6):12873-12892. https://doi.org/10.3390/ijms140612873
Chicago/Turabian StyleLi, Yuling, Zhijun Duan, Yan Tian, Zhen Liu, and Qiuming Wang. 2013. "A Novel Perspective and Approach to Intestinal Octreotide Absorption: Sinomenine-Mediated Reversible Tight Junction Opening and Its Molecular Mechanism" International Journal of Molecular Sciences 14, no. 6: 12873-12892. https://doi.org/10.3390/ijms140612873