Arachidonic acid increases inositol phospholipid metabolism and glutamate release in synaptosomes prepared from hippocampal tissue.
We have been interested in the possibility that arachidonic acid or one of its 12-lipoxygenase metabolites may function as a retrograde messenger in long-term potentiation (LTP) in the dentate gyrus of the hippocampus. One criterion required of a retrograde messenger is that it stimulates presynaptic changes. Here, two possible presynaptic actions of arachidonic acid and its 12-lipoxygenase metabolites, 12-hydroxyeicosatetraenoic acid (HETE) and 12-hydroperoxyeicosatetraenoic acid (HPETE), are examined. We report that arachidonic acid, HETE, and HPETE significantly increase both K(+)-stimulated release of [3H]glutamate and [3H]inositol labelling of inositol phosphates in synaptosomes, whereas other biologically important fatty acids (oleic, palmitic, and stearic) failed to induce a similar response. The findings of these experiments are consistent with the hypothesis that arachidonic acid, HETE, or HPETE may play the role of a retrograde messenger in LTP.
Lynch
M A
MA
National Institute for Medical Research, London, England.
Voss
K L
KL
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D015289:Leukotrienes / Q000494:pharmacology; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism
D001095:Arachidonic Acids; D005227:Fatty Acids; D005971:Glutamates; D006893:Hydroxyeicosatetraenoic Acids; D007295:Inositol Phosphates; D015289:Leukotrienes; D010716:Phosphatidylinositols; D016718:Arachidonic Acid; D018698:Glutamic Acid; D007294:Inositol; C021201:12-HPETE; D011188:Potassium