MDR1 IN TASTE-BUDS OF RAT VALLATE PAPILLA - FUNCTIONAL, IMMUNOHISTOCHEMICAL, AND BIOCHEMICAL-EVIDENCE

Multidrug resistance P-glycoprotein (MDR1) is a membrane protein of 15 0-170 kDa that catalyzes the ATP-driven efflux of hydrophobic xenobiot ics, including fluorescent dyes, from cells. Expressed in many epithel ial tissues and in the endothelia of the blood-brain barrier, the MDR1 protein provides major routes of detoxification. We found that taste cells of the rat vallate papilla (VP; posterior tongue) had only a slo w increase in fluorescence due to uptake of the hydrophobic dye calcei n acetoxymethyl ester. However, the development of fluorescence was ac celerated two- to threefold by substrates and/or inhibitors of MDR1, s uch as verapamil, tamoxifen, and cyclosporin A, and by addition of the transport-blocking antibody to MDR1, UIC2, Western blots of vallate t issue rich in taste buds with the MDR1-specific monoclonal antibodies C219 and C494 revealed an immunoreactive protein at similar to 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 tissue sections, MDR1-like immunoreactivity was fou nd in taste cells, These results show that MDR1 is present and functio nal in vallate taste cells of the rat. MDR1-related transport may achi eve active elimination of xenobiotics from the sensory cells and there by protect the peripheral taste organs from potentially harmful molecu les contained in an animal's food.