SIMULTANEOUS INVITRO MEASURMENT OF INTESTINAL TISSUE PERMEABILITY ANDTRANSEPITHELIAL ELECTRICAL-RESISTANCE (TEER) USING SWEETANA GRASS DIFFUSION CELLS

A simple modification of the commercially available Sweetana-Grass (S- G) side-by-side diffusion cells, allowing the simultaneouS measurement of tissue permeability and transepithelial electrical resistance (TEE R), has been described and validated for rat excised, muscle-free inte stinal tissue. The TEER-lowering effects of a series of acylcarnitines were shown to be correlated with previously reported in vitro (i.e.. membrane perturbation) and in vivo (i.e., absorption enhancement) acti vity. The TEER-lowering effect of palmitoyl carnitine chloride (PCC) w as also shown to be reversible. The effects of PCC on TEER and the per meability of poorly absorbed compounds (cefoxitin and lucifer yellow) were simultaneously determined. Compared to controls (mannitol-treated ). PCC immediately produced a rapid drop in colon TEER. By 5 min post- PCC addition, colon TEER was 50% of control; by 10 min post-PCC additi on. colon TEER was 17% of control. After a lag of about 5-10 min post- PCC addition, the cefoxitin or lucifer yellow permeability coefficient increased more than 20-fold. The modified S-G cells provide a simple and reproducible method whereby flux and TEER can be simultaneously de termined, providing a valuable link between the effect of absorption e nhancers on TEER measurements and the increased permeability of poorly absorbed compounds.