Inhibition of gap junction-mediated intercellular communication by alpha-linolenate.

The purpose of this investigation was to assess whether alterations in the fatty acid composition of rat liver epithelial (WB-F344) cell phospholipids would modulate gap junction-mediated intercellular communication (GJIC). WB-F344 cells were grown to confluency in culture medium supplemented with one of seven different fatty acids at a concentration of 50 microM for 48 h. Only alpha-linoleate (18:3 n-3) significantly inhibited GJIC. Saturated fatty acids (12:0, 16:0, and 18:0), a monounsaturated fatty acid (18:1 n-9), and n-6 polyunsaturated fatty acids (18:2 and 20:4) did not affect GJIC. The alpha-linolenate-induced inhibition of GJIC was not due to the activation of protein kinase C or intracellular hydroperoxide production, two lipid-dependent parameters previously shown to inhibit GJIC. In addition, alpha-linolenate did not alter membrane fluidity. Although the mechanism by which alpha-linolenate inhibits GJIC is unclear, changes in the fatty acid composition of cell phospholipids may be of critical importance. Subsequent to supplementation with alpha-linolenate, WB-F344 cell phospholipids had reduced 20:4 n-6 and elevated n-3 fatty acids. The results of this investigation emphasize the importance of current research into the influence of lipids on cell function and identify a new mechanism by which gap junctions can be modulated.