Protein expression pattern of P-glycoprotein along the gastrointestinal tract of the Yucatan micropig
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Published on: December 17, 2011
Huadong Tang1, Yvonne Pak, Michael Mayersohn
1Department of Pharmacy Practice and Science, Arizona Center for Phytomedicine Research, College of Pharmacy, The University of Arizona, Tucson, AZ 85721, USA.
Abstract:
The purpose of this study is to characterize the distribution pattern of P-gp protein levels along the entire GI tract in the Yucatan micropig, which is being developed as a model for human drug bioavailability. Small and large intestines were freshly obtained and divided into about 37 segments and 10 segments, respectively (ca., 1 foot/segment). Epithelial cells from the small intestine were obtained by an elution method; whereas, a scraping method was applied to the large intestine. Total cellular protein was isolated from the epithelial cells. Western blot analysis using P-gp antibody showed that the amount of P-gp protein increased distally from the duodenum to the ileum over approximately a 10-fold range. P-gp protein in the large intestine was present at a higher level in the central portion, but the absolute amount was much less than what was found in the small intestine.
Insights
P-glycoprotein (P-gp) levels increase along the Yucatan micropig
Area of Science:
- Pharmacology
- Gastroenterology
- Animal Models
Background:
- Yucatan micropigs are a developing model for human drug bioavailability studies.
- Understanding drug transporter distribution is crucial for predicting absorption and efficacy.
- P-glycoprotein (P-gp) significantly influences drug absorption and efflux.
Purpose of the Study:
- To map the distribution of P-gp protein across the entire gastrointestinal (GI) tract of the Yucatan micropig.
- To establish the Yucatan micropig as a relevant preclinical model for drug disposition studies.
Main Methods:
- Harvesting and segmenting the small and large intestines of Yucatan micropigs.
- Isolating epithelial cells using elution (small intestine) and scraping (large intestine) methods.
- Quantifying P-gp protein levels via Western blot analysis.
Main Results:
- P-gp protein expression demonstrated a significant distal increase from duodenum to ileum in the small intestine (approx. 10-fold range).
- Higher P-gp levels were observed in the central portion of the large intestine compared to its ends.
- Absolute P-gp amounts in the large intestine were considerably lower than in the small intestine.
Conclusions:
- The Yucatan micropig exhibits a distinct, segment-specific distribution pattern of P-gp in the GI tract.
- This characterized P-gp distribution supports the Yucatan micropig's utility in preclinical drug bioavailability research.
- Findings provide essential data for pharmacokinetic modeling and drug development using this animal model.
