Reciprocal Regulation of Fatty Acid Release In The Brain By Gaba and Glutamate
Free fatty acids (FFA) and their metabolites have many effects on neurochemical processes, including altering receptor-effector coupling, modulating the activity of protein kinase C, and changing ion channel conductance in the cell membrane. However, the neurotransmitters and other factors that control the release of FFA in neurons in normal or pathological states are not well defined. The following studies investigate the regulation of FFA release in intact brain, synaptosomes, and isolated neurons in culture in response to drugs that interact at γ-aminobutyric acid (GABA) and glutamate receptors. The results suggest that neuronal excitation via stimulation of glutamate receptors or blockade of GABA receptors causes the activation of FFA release, and that phosphatidylcholine (PC) is a major source of FFA. Conversely, inhibition of neuronal activity reduces FFA release. FFA release occurs via activation of phospholipase A2 and possibly via activation of a PC-specific phospholipase C, followed by diacylglycerol (DG) lipase. The common pathway for these effects may be alterations in intracellular calcium.
KeywordsFree Fatty Acid Arachidonic Acid Hippocampal Neuron Kainic Acid Free Fatty Acid Level
Unable to display preview. Download preview PDF.
- Bazan NG, Birkle DL, Tang W, Reddy TS (1986) The accumulation of free arachidonic acid, diacylglycerols, prostaglandins and lipoxygenase reaction products in the brain during experimental epilepsy. In: Advances in Neurology, Vol 44 (Delgado-Escueta AV, Ward AA, Woodbury DM, Porter RJ, eds) pp 879–902. New York: Raven Press.Google Scholar
- Birkle DL, Kurian P, Bazan NG (1988a) Seizure-induced alterations in lipid metabolism in hippocampus and cerebral cortex. Soc Neurosci Abstr 14: 574.Google Scholar
- Conn PM (1990) Methods in neuroscience, Vol 2: Cell culture. San Diego: Academic Press Inc.Google Scholar
- El-Fakahany EE, Alger BE, Lai WS, Pitler TA, Worley PF, Baraban JM (1990) Neuronal muscarinic responses: Role of protein kinase C. FASEB J 2: 2575–2583.Google Scholar
- Flynn CJ, Birkle DL, Wecker L (1986) Diazepam prevents seizure-induced increases in free fatty acids and choline in rat cerebrum. Soc Neurosci Abstr 12: 454–454.Google Scholar
- Martinson EA, Goldstein D, Heller Brown J (1990) Muscarinic receptor activation of phosphatidylcholine hydrolysis: Relationship to phosphoinositide hydrolysis and diacylglycerol metabolism. J Biol Chem 264: 14748–14754.Google Scholar
- Reddy TS and Bazan NG (1987) Arachidonic acid, stearic acid and diacylglycerol accumulation correlates with the loss of phosphatidylinositol 4,5-bisphosphate in cerebrum two seconds after electroconvulsive shock: Complete reversion of changes 5 minutes after stimulation. J Neurosci Res 18: 449–455.PubMedCrossRefGoogle Scholar
- Rodriguez de Turco EB, Morelli de Liberti S, Bazan NG (1983) Stimulation of free fatty acid and diacylglycerol accumulation in cerebrum and cerebellum during bicuculline-induced status epilepticus: Effect of pre-treatment with alpha-methyl-p-tyrosine and p-chlorophenylalanine. J Neurochem 40: 252–259.PubMedCrossRefGoogle Scholar
- Shahar A, deVellis J, Vernadakis A, Haber B (1989) A dissection and tissue culture manual of the nervous system. New York: Alan R. Liss, Inc.Google Scholar