ARACHIDONIC-ACID REVERSIBLY REDUCES INTER CELLULAR JUNCTION PERMEABILITY

The effect of arachidonic acid on intercellular coupling via gap junct ions has been studied in BICR/M1R(k) cells - a mammary tumor cell line of the Marshall rat. Arachidonic acid is shown to reversibly block bo th ionic and dye coupling in a dose-dependent manner. The cells recoup led after the washout with either serum- or albumin (essentially fatty acid-free)-containing solution. The intracellular pH decreased from 7 ,2 to 7,0 after arachidonic acid treatment; the same pH shift in the a bsence of arachidonic acid, however, had no effect on the junctional p ermeability. Flow cytometric measurements revealed an arachidonic acid -induced increase in the cytoplasmic free Ca2+ concentration which was also reversible upon albumin treatment. Intracellular Ca2+ or H+ are unlikely to be involved in the mechanism of the arachidonic acid effec t on intercellular coupling: high resolution measurements using double whole-cell technique also show reversible blockage of the junctional conductance in the presence of arachidonic acid while the pipette solu tion was buffered with 10 mM HEPES and 10 mM EGTA lo clamp intracellul ar calcium and proton concentrations. We suggest that arachidonic acid directly affects the pp junction channels, probably interfering with the lipid-protein interactions.