PURPOSE: Using primary cultured rabbit oral mucosal epithelial cells (ROEpi), we investigated whether carrier-mediated drug absorption via the oral mucosal route occurs. METHODS: Oral mucosal epithelial cells were isolated from rabbit buccal mucosa and cultured on tissue culture plates. When the cells reached confluence, drug uptake experiments were performed. [14C]Benzoic acid or [14C]acetic acid was used as a marker for monocarboxylic acid carrier-mediated transport. RESULTS: The uptake of [14C]benzoic acid by ROEpi occurred at a much lower rate at 4 degrees C than at 37 degrees C. The metabolic inhibitors, sodium azide and 2,4-dinitrophenol, significantly inhibited the uptake of [14C]benzoic acid by ROEpi. Various monocarboxylic acids inhibited the uptake of [14C]benzoic acid or [14C]acetic acid by ROEpi, whereas dicarboxylic acids did not affect the uptake. Kinetic analysis using Lineweaver-Burk plots revealed that acetic acid competitively inhibited the uptake of [14C]benzoic acid, and benzoic acid competitively inhibited the uptake of [14C]acetic acid by ROEpi. CONCLUSIONS: There exists a carrier-mediated transport system for monocarboxylic acids in oral mucosal epithelial cells.
PURPOSE: Using primary cultured rabbit oral mucosal epithelial cells (ROEpi), we investigated whether carrier-mediated drug absorption via the oral mucosal route occurs. METHODS: Oral mucosal epithelial cells were isolated from rabbit buccal mucosa and cultured on tissue culture plates. When the cells reached confluence, drug uptake experiments were performed. [14C]Benzoic acid or [14C]acetic acid was used as a marker for monocarboxylic acid carrier-mediated transport. RESULTS: The uptake of [14C]benzoic acid by ROEpi occurred at a much lower rate at 4 degrees C than at 37 degrees C. The metabolic inhibitors, sodium azide and 2,4-dinitrophenol, significantly inhibited the uptake of [14C]benzoic acid by ROEpi. Various monocarboxylic acids inhibited the uptake of [14C]benzoic acid or [14C]acetic acid by ROEpi, whereas dicarboxylic acids did not affect the uptake. Kinetic analysis using Lineweaver-Burk plots revealed that acetic acid competitively inhibited the uptake of [14C]benzoic acid, and benzoic acid competitively inhibited the uptake of [14C]acetic acid by ROEpi. CONCLUSIONS: There exists a carrier-mediated transport system for monocarboxylic acids in oral mucosal epithelial cells.