The effect of omega-3 fatty acids on Ca-ATPase in rat cerebral cortex.
Neuronal Ca-ATPase has the essential function of keeping intracellular Ca levels in the micromolar range. This is a prerequisite for normal neurotransmission. This study was designed to determine whether Ca-ATPase is a target for docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) action: results show that both these fatty acids are inhibitors of Ca-ATPase activity in synaptosomal membranes isolated from rat cerebral cortex (-65+/-5% at [DHA]=20 microg/ml, -59+/-7% at [EPA]=20 microg/ml). The inhibition caused by EPA, but not that of DHA, could be reversed completely by the addition of calphostin, a protein kinase C blocker. In contrast, DHA could stimulate Ca-ATPase activity (+132+/-5% at [DHA]=30 microg/ml) only in calmodulin-depleted membranes. In addition, Na,K-ATPase (which drives the Na-Ca exchanger) was inhibited by both DHA and EPA, both at 30 microg/ml (-15+/-0.7% and -42+/-1%, respectively). These results suggest a mechanism that explains the dampening effect of omega-3 fatty acids on neuronal activity.
Kearns
S D
SD
Department of Physiology, University of Pretoria, South Africa.
Haag
M
M
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology*; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D015525:Fatty Acids, Omega-3; D009281:Naphthalenes; C061465:calphostin complex; D004281:Docosahexaenoic Acids; D000252:Calcium-Transporting ATPases; D002118:Calcium