Effects of diacylglycerols on LLC-PK1 renal epithelia: similarity to phorbol ester tumor promoters.

As previously shown using phorbol ester tumor promoters (see Mullin and O'Brien: Am. J. Physiol., 251:C597-C602, 1986), diacylglycerols induce leakiness in LLC-PK1 renal epithelial tight junctions. The similarity between phorbol ester and diacylglycerol action includes effects on 1) cell morphology, 2) dome formation, 3) transepithelial resistance and potential difference, 4) transepithelial flux of D-mannitol, and 5) mitogenesis. Four diacylglycerols have been tested: 1,2-dioctanoylglycerol; 1,2-dicaprylglycerol; 1,2-dioleoylglycerol; and 1-oleoyl-2-acetoyl-sn-3-glycerol. Their relative effectiveness depended upon the phenomenon being observed. Unlike phorbol esters, diacylglycerol effects were reversible within hours at 37 degrees C in the continued presence of diacylglycerol, and effects were more pronounced when cell sheets were exposed to diacylglycerols from the basolateral cell surface. Overall, these findings indicate that previous results with phorbol esters may be attributed to the protein kinase C signal transduction system, and this system may therefore exert a role in transepithelial permeability.