Epithelial cell membrane, negative charged

Apart from causing very well known cardiotoxic effects, phenothiazine derivatives can accumulate in lung epithelial cell membranes and therefore cause severe respiratory disorders. In the study performed by Ito et al. [279] it was found that CPZ (9) inhibited transepithelial Cl transport, mainly due to two mechanisms influence on the beta-adrenergic receptor and inhibition of basolateral potassium channels. The authors of this study also suggested that the recorded effects could result from the electrostatic interactions between the drug molecules and negatively charged components of the inner leaflet of the plasma membrane. 

Figure 2.5 Schematic of the structure of epithelial cells, based on several literature sources [55,63,69,73,74,76,78,79]. The tight junctions and the basement membrane appear to be slightly ion-selective (lined with some negatively charged groups) [75,76,79]. [Avdeef, A., Curr. Topics Med. Chem., 1, 277-351 (2001). Reproduced with permission from Bentham Science Publishers, Ltd.]...

As P-gp, BCRP is located at the apical membrane of epithelial cells in the intestine, kidney and placenta (Schinkel Jonker, 2003) (Fig. 1). Regarding substrate profiles, BCRP shows some overlap with P-gp and MRPl but does not confer resistance to taxols, cis-platin and verapamil, or vinca alkaloids and anthracyclines. On the other hand, BCRP is lotown for transporting positively and negatively charged drugs (Sharom, 2008). 

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