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. [H -3]Norepinephrine release evoked by carbachol was unaffected by the mo difications. Basal spontaneous release was elevated with increases in the degree of unsaturation using cells supplemented with n-3 fatty aci ds; a reverse correlation was observed for [H-3]norepinephrine uptake. Supplementation of PC12 cells with either n-6 fatty acids or 18:1 als o increased the basal release and decreased the uptake. Docosahexaenoi c acid promoted and arachidonic acid suppressed neurite outgrowth indu ced by nerve growth factor. Choline acetyltransferase activity was sli ghtly influenced by these fatty acids. Thus, modifications of PC1Z cel ls with arachidonic acid and docosahexaenoic acid had a relatively sma ll effect on the degree of differentiation but had pronounced but oppo site effects on neurite elongation. Ethanolamine glycerophospholipid s ynthesis was elevated during differentiation induced by nerve growth f actor and it was suppressed by added arachidonic acid but not by docos ahexaenoic acid. Our results raise the possibility that the decreased phospholipid synthesis caused by arachidonate may lead to the suppress ion of neurite elongation.