Transcellular electrical resistance

Generally, low molecular mass permeation enhancers can be divided into transcellular and paracellular permeation enhancers. On the one hand the potential of permeation enhancers to open the paracellular route of uptake can be determined by the reduction in the transepithelial electrical resistance (TEER) (enhancement potential = EP). On the other hand the potential of permeation enhancers to open the transcellular route of uptake can be determined by the lactate dehydrogenase (LDH) assay (LDH potential = LP). The parameter K = (EP—LP)/EP represents the relative contribution of the paracellular pathway. Consequently, a K value of 0 means predominantly transcellular and a K value of 1 means predominantly paracellular. Based on this classification system Whitehead and Mitragotri classified over 50 low molecular mass permeation enhancers showing that most of them are paracellular and only a few of them are transcellular permeation enhancers (2008). 

The main component of the blood-brain barrier is the brain endothelium, which exhibits a physical, an efflux and a metabolic barrier for the transport of drugs into the CNS. The physical barrier, an efflux, is a result of the tight junctions between adjacent endothelial cells, which are around 50-100 times tighter than in the peripheral endothelium, so that penetration across the endothelium is effectively confined to transcellular mechanisms [26, 27]. These junctions significantly restrict even the movement of small ions such as Na" " and Cl , so that the transendothelial electrical resistance (TEER), which is typically 2-20 2 cm in peripheral capillaries, can be over 1000 1 cm in brain endothelium [28]. 

This buffer is used in both the unidirectional (permeability) and the bidirectional (Efflux, Section 4.3.2). In the permeability assay, NCEs are placed into the apical compartment of the Transwell. Duplicate samples are taken immediately after compound addition from the apical compartment (zero time) and then after 2h from both the apical and basolateral compartments for LC-MS/MS analysis. The integrity of the monolayer is confirmed by the measurement of the transepithelial electrical resistance (TEER), which must be above a certain limit to be used for transport experiments. In addition, with each experiment a transcellular and a paracellular marker are included for quality control. 

These are just some examples that demonstrate the complexity of the processes involved in intestinal absorption other parameters that need to be taken into consideration when studying intestinal transport include transepithelial electrical resistance (TEER), active efflux pumps (such as P-gp), passive transcellular and paracellular diffusion. 

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