MECHANISMS OF GLIAL SWELLING BY ARACHIDONIC-ACID

The effect of arachidonic acid (AA, 20:4) was analyzed in vitro by emp loyment of C6 glioma cells and astrocytes from primary culture. The ce lls were suspended in an incubation chamber under continuous control o f pH, pO2, and temperature. Cell swelling was quantified by flow cytom etry. After a control period, the suspension was added with AA at conc entrations of 0.01 to 1.0 mM. Administration of AA induced an immediat e, dose dependent swelling in C6 glioma cells or astrocytes. AA-concen trations of 0.01 mM led to an increase of the glial cell volume to 103 .0 +/- 1.0% of control, 0.1 mM to 110.0 +/- 1.5%, and 1.0 mM to 118.8 +/- 1.5% within 10 min. The swelling response to linoleic acid (18 : 2 ) was only about half of what was found when AA was administered at a concentration of 0.1 mM, whereas stearic acid (18 : 0) did not induce any cell volume changes. Inhibition of the cyclo- and lipoxygenase pat hway by BW 755C did not prevent glial swelling from AA, whereas it was reduced by SOD, or almost completely abolished by the aminosteroid U- 74389F, an antagonist of lipid peroxidation. Replacement of Na+- and C l--ions in the suspension medium by choline chloride was also associat ed with complete abolishment of cell swelling from AA. The results dem onstrate an impressive efficacy of arachidonic acid to induce glial sw elling which might be attributable to activation of lipid peroxidation by the fatty acid, leading to an increased Na+-permeability and subse quent influx of water into the cells.