MDR1 in taste buds of rat vallate papilla: functional, immunohistochemical, and biochemical evidence

Multidrug resistance P-glycoprotein (MDR1) is a membrane proteinof 150-170 kDa that catalyzes the ATP-driven efflux of hydrophobic xenobiotics, including fluorescent dyes, from cells. Expressed in manyepithelial tissues and in the endothelia of the blood-brain barrier,the MDR1 protein provides major routes of detoxification. We found thattaste cells of the rat vallate papilla (VP; posterior tongue) had onlya slow increase in fluorescence due to uptake of the hydrophobic dyecalcein acetoxymethyl ester. However, the development of fluorescencewas accelerated two- to threefold by substrates and/orinhibitors of MDR1, such as verapamil, tamoxifen, and cyclosporin A,and by addition of the transport-blocking antibody to MDR1, UIC2.Western blots of vallate tissue rich in taste buds withthe MDR1-specific monoclonal antibodies C219 and C494 revealed animmunoreactive protein at ~170 kDa. In contrast, the lingual epithelium surrounding the VP showed a much weaker band with these antibodies. Furthermore, using the antibodies C494 and UIC2 with tissuesections, MDR1-like immunoreactivity was found in taste cells. Theseresults show that MDR1 is present and functional in vallate taste cellsof the rat. MDR1-related transport may achieve active elimination ofxenobiotics from the sensory cells and thereby protect the peripheraltaste organs from potentially harmful molecules contained in ananimal's food.