Analysis of Carrier-Mediated Transport Systems in Drug Absorption from Oral Mucosa

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The in vitro uptake study was performed using the isolated cells of human oral mucosa, buccal and the dorsum of tongue, to investigate the mechanisms of glucose and oligopeptide uptake. The uptake of D-glucose was much larger in cells of the dorsum of tongue than in buccal cells and was inhibited more extensively by 2-deoxy-D-glucose, a substrate of facilitative glucose transporters, than by α-methyl-D-glucoside, a specific substrate of SGLT1, suggesting the larger contribution of facilitative transporter than NaィイD1+ィエD1/glucose cotransporter. Furthermore, from the results of inhibition studies by the several sugar analogues including maltose and D-mannose, GLUT1 and/or GLUT3 were suggested to take part in the glucose uptake by oral mucosa. Therefore, we have attempted to confirm the expression of glucose transporters on the oral mucosa by employing Western blotting. As a result, it was suggested that SGLT1, GLUT1, GLUT2 and GLUT3 are expressed in the epithelial cells of human oral mucosa. The result of the uptake study of glycylsarcosine, a model dipeptide, by isolated oral cells showed the presence of carrier-mediated transport systems for oligopeptides in human oral mucosal cells. The transport of D-glucose and glycylsarcosine across stratified cell layer of cultured human oral mucosal cells was also examined, and the results showed that the transporters function not only for the uptake of these substrates by the mucosal cells but also for the transport across the stratified mucosal cell layers.