Membrane fatty acid modifications of PC12 cells by arachidonate or docosahexaenoate affect neurite outgrowth but not norepinephrine release.

The relationships between membrane fatty acid modification and neurite outgrowth and norepinephrine release were evaluated in PC12 cells. [3H]Norepinephrine release evoked by carbachol was unaffected by the modifications. Basal spontaneous release was elevated with increases in the degree of unsaturation using cells supplemented with n-3 fatty acids; a reverse correlation was observed for [3H]norepinephrine uptake. Supplementation of PC12 cells with either n-6 fatty acids or 18:1 also increased the basal release and decreased the uptake. Docosahexaenoic acid promoted and arachidonic acid suppressed neurite outgrowth induced by nerve growth factor. Choline acetyltransferase activity was slightly influenced by these fatty acids. Thus, modifications of PC12 cells with arachidonic acid and docosahexaenoic acid had a relatively small effect on the degree of differentiation but had pronounced but opposite effects on neurite elongation. Ethanolamine glycerophospholipid synthesis was elevated during differentiation induced by nerve growth factor and it was suppressed by added arachidonic acid but not by docosahexaenoic acid. Our results raise the possibility that the decreased phospholipid synthesis caused by arachidonate may lead to the suppression of neurite elongation.