P-glycoprotein in intestines, liver, kidney and lymphocytes in horse.

The research focuses on understanding the role and location of P-glycoprotein (P-gp), a drug transporter protein, in various cells in horses. The expression of P-gp and its related gene were studied in cells such as intestinal cells, liver cells, kidney cells, and lymphocytes. The research also involved comparing the P-gp protein sequence in horses to other species.

P-gp Localization and Expression in Different Cells

• The researchers observed the P-gp protein and its related gene in various cells of horses, including intestinal cells (enterocytes), liver cells (hepatocytes), kidney cells (renal tubular cells), blood cells (lymphocytes), and cells in the intestines’ lining (intestinal intraepithelial).
• P-gp protein and gene were found in all parts of the horse’s intestine as revealed by Real-time RT-PCR and Western blot tests. However, the research found no specific correlation between the gene and protein expression.
• Through immunohistochemistry, researchers localized P-gp to the apical cell membranes of enterocytes and found staining in the intestinal intraepithelial and lamina propria lymphocytes.
• Peripheral blood lymphocytes were also stained with P-gp, and researchers observed the gene and protein expression of P-gp in these cells.

Expression and Role of P-gp in Liver and Kidney

• The study showed high P-gp gene and protein expression in the horse liver. The liver cells’ bile canalicular membranes had P-gp immunoreactivity.
• In the kidneys, researchers noted the gene and protein expression of P-gp with the protein’s localization in different parts of the nephrons.
• The expression of P-gp in the liver and kidneys indicates its role in the distribution and excretion of substrate compounds, impacting the oral bioavailability of drugs.

Protein Sequence Comparison and Insertions

• The study compared the P-gp protein sequence in horses with that of other species. The comparison revealed two specific amino acid insertions at the N-terminal region of the horse P-gp that were not present in other examined species.
• One of the insertions was a 99 amino acid long sequence inserted at amino acid positions 23-121 from the N-terminal. The second one was a six amino acid sequence present at positions 140-145 from the N-terminal.

The findings may influence the understanding of how P-gp affects drug transport, bioavailability, and excretion in horses, making it essential for drug dosage and therapy design.