THE EFFECTS OF TELEOCIDIN AND APLYSIATOXIN TUMOR PROMOTERS ON EPITHELIAL TIGHT JUNCTIONS AND TRANSEPITHELIAL PERMEABILITY - COMPARISON TO PHORBOL ESTERS

Control of transepithelial permeability by regulation of tight junctions is exerted by the non-phorbol ester tumor promoters, teleocidin and aplysiatoxin. Similar to the phorbol esters, tetradecanoylphorbol-13-acetate (TPA) and phorbol dibutyrate (PDBU), both teleocidin and aplysiatoxin cause a reversible decrease of transepithelial voltage and transepithelial resistance across LLC-PK1 renal epithelial cell sheets at concentrations as low as 10-8M. These compounds are effective from either side of these polar epithelial cells, i.e. apical or basolateral. The decreases in transepithelial gradients and resistance are paralleled by a rise in the transepithelial (paracellular) flux of D-mannitol between the cells (through the tight junctions). These four tumor promoters, TPA, PDBU, teleocidin and aplysiatoxin, are all known protein kinase C activators, and support the case for proteinkinase-C-mediated control of tight junctional permeability. © 1990 Oxford University Press.