Reciprocal Regulation of Fatty Acid Release In The Brain By Gaba and Glutamate

  • Dale L. Birkle
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 318)

Abstract

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.

Keywords

Serotonin Retina Prostaglandin Norepinephrine Choline 

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References

  1. Andrade R, Malenka RC, Nicoll RA (1986) A G protein couples serotonin and GABAB receptors to the same channels in hippocampus. Science 234: 1261–1265.PubMedCrossRefGoogle Scholar
  2. Baraldi M, Guidotti A, Schwartz JP, Costa E (1979) GABA receptors in clonal cell lines: A model for study of benzodiazepine action at molecular level. Science 205: 821–823.PubMedCrossRefGoogle Scholar
  3. Bazan NG (1970) Effects of ischemia and electroconvulsive shock on free fatty acid pool in the brain. Biochim Biophys Acta 218: 1–10.PubMedCrossRefGoogle Scholar
  4. 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
  5. Birkle DL and Bazan NG (1984) Effect of K+ depolarization on the synthesis of prostaglandins, hydroxyeicosatetraenoic acid (HETE) and other eicosanoids in the rat retina: Evidence for esterification of 12-HETE in lipids. Biochim Biophys Acta 795: 564–573.PubMedCrossRefGoogle Scholar
  6. Birkle DL and Bazan NG (1987) Effect of bicuculline-induced status epilepticus on prostaglandins and hydroxyeicosatetraenoic acids in rat brain subcellular fractions. J Neurochem 48: 1768–1778.PubMedCrossRefGoogle Scholar
  7. Birkle DL and Bazan NG (1988) Cerebral perfusion of metabolic inactivators: A new method for rapid fixation of labile lipid pools in brain. Neurochem Res 13: 849–852.PubMedCrossRefGoogle Scholar
  8. Birkle DL and Ellis EF (1983) Conversion of arachidonic acid to cyclooxygenase and lipoxygenase reaction products and incorporation into phospholipids in the mouse neuroblastoma clone, Neuro-2A. Neurochem Res 8: 319–332.PubMedCrossRefGoogle Scholar
  9. Birkle DL and Wiley KS (1991) Bicuculline induces free fatty acid release from phospholipids in Neuro-2A cells in culture. Neurochem Res 16: 1285–1293.PubMedCrossRefGoogle Scholar
  10. 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
  11. Birkle DL, Kurian P, Braquet P, Bazan NG (1988b) The platelet activating factor antagonist, BN52021, decreases accumulation of free polyunsaturated fatty acids in mouse brain during ischemia and electroconvulsive shock. J Neurochem 51: 1900–1905.PubMedCrossRefGoogle Scholar
  12. Carlen PL, Gurevich N, Wu PH, Su WG, Corey EJ, Pace-Asciak CR (1989) Actions of arachidonic acid and hepoxilin A3 on mammalian hippocampal CA1 neurons. Brain Res 497: 171–176.PubMedCrossRefGoogle Scholar
  13. Channon JY and Leslie CC (1990) A calcium-dependent mechanism for associating a soluble arachidonoyl-hydrolyzing phospholipase A2 with membrane in the macrophage cell line RAW 264.7. J Biol Chem 265, 5409–5413.PubMedGoogle Scholar
  14. Conn PM (1990) Methods in neuroscience, Vol 2: Cell culture. San Diego: Academic Press Inc.Google Scholar
  15. de Belleroche JS and Bradford HF (1972) Metabolism of beds of mammalian cortical synaptosomes: Response to depolarizing influences. J Neurochem 19: 585–602.PubMedCrossRefGoogle Scholar
  16. Diaz-Laviada I, Larrodera P, Diaz-Meco MT (1990) Evidence for a role of phosphatidylcholine-hydrolysing phospholipase C in the regulation of protein kinase C by rasand srconcogenes. EMBO J 9: 3907–3912.PubMedGoogle Scholar
  17. Dorman RV (1991) PGF synthesis in isolated cerebellar glomeruli: Effects of membrane depolarization, calcium availability and phospholipase activity. Prostaglandins Leukot Essent Fatty Acids 42: 233–240.PubMedCrossRefGoogle Scholar
  18. Duman RS, Karbon EW, Harrington C, Enna SJ (1986) An examination of the involvement of phospholipases A2 and C in the alpha-adrenergic and GABA receptor modulation of cAMP accumulation. J Neurochem 47: 800–810.PubMedCrossRefGoogle Scholar
  19. Dumuis A, Pin JP, Oomagari K, Sebben M, Bockaert J (1990) Arachidonic acid released from striatal neurons by joint stimulation of ionotropic and metabotropic quisqualate receptors. Nature 347, 182–184.PubMedCrossRefGoogle Scholar
  20. Dumuis A, Sebben M, Haynes L, Pin J-P, Bockaert J (1988) NMD A receptors activate the arachidonic acid cascade system in striatal neurons. Nature 336: 68–70.PubMedCrossRefGoogle Scholar
  21. 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
  22. Exton JH (1990) Hormonal regulation of phosphatidylcholine breakdown. Adv Second Messenger Phosphoprotein Res 24: 152–157.PubMedGoogle Scholar
  23. Felder CC, Kanterman RY, Ma AL, Axelrod J (1990) Serotonin stimulates phospholipase A2 and the release of arachidonic acid in hippocampal neurons by a type 2 serotonin receptor that is independent of inositolphospholipid hydrolysis. Proc Natl Acad Sci USA 87: 2187–2191.PubMedCrossRefGoogle Scholar
  24. 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
  25. Freeman EJ, Terrian DM, Dorman RV (1990) Presynaptic facilitation of glutamate release from isolated hippocampal mossy fiber nerve endings by arachidonic acid. Neurochem Res 15: 743–750.PubMedCrossRefGoogle Scholar
  26. Furuya S, Ohmori H, Shigemoto T, Sugiyama H (1989) Intracellular calcium mobilization triggered by a glutamate receptor in rat cultured hippocampal cells. J Physiol 414: 539–548.PubMedGoogle Scholar
  27. Ho AK and Klein DC (1987) or treatment with intracellular free Ca2+ elevating agents increases pineal phospholipase A2 activity. J Biol Chem 262: 11764–11770.PubMedGoogle Scholar
  28. Innis RB, Nestler EJ, Aghajanian GK (1988) Evidence for G protein mediation of serotonin-and GABAB-induced hyperpolarization of rat dorsal raphe neurons. Brain Res 459: 27–36.PubMedCrossRefGoogle Scholar
  29. Kanterman RY, Ma AL, Briley EM, Axelrod J, Felder CC (1990) Muscarinic receptors mediate the release of arachidonic acid from spinal cord and hippocampal neurons in primary culture. Neurosci Lett 118: 235–237.PubMedCrossRefGoogle Scholar
  30. Kim D and Clapham, DE (1989) Potassium channels in cardiac cells activated by arachidonic acid and phospholipids. Science 244: 1174–1176.PubMedCrossRefGoogle Scholar
  31. Kim D and Duff RA (1990) Regulation of K+ channels in cardiac myocytes by free fatty acids. Circ Res 67: 1040–1046.PubMedCrossRefGoogle Scholar
  32. Kim D, Lewis DL, Graziadei L, Neer EJ, Bar-Sagi D, Clapham DE (1989) G-protein beta-gamma subunits activate the cardiac muscarinic K+-channel via phospholipase A2. Nature 337: 557–560.PubMedCrossRefGoogle Scholar
  33. Lands W and Crawford C (1976) Enzymes of membrane phospholipid metabolism in animals. In: Enzymes of biological membranes (Martonosi A, eds) pp 3–85. New York: Plenum Press.CrossRefGoogle Scholar
  34. Lazarewicz JW, Wroblewski JT, Costa E (1990) N-methyl-D-aspartate-sensitive glutamate receptors induce calcium-mediated arachidonic acid release in primary cultures of cerebellar granule cells. J Neurochem 55: 1875–1881.PubMedCrossRefGoogle Scholar
  35. London ED and Coyle JT (1979) Specific binding of [3H]kainic acid to receptor sites in rat brain. Mol Pharmacol 15: 492–505.PubMedGoogle Scholar
  36. 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
  37. Massicotte G, Oliver MW, Lynch G, Baudry M (1990) Effect of bromophenacyl bromide, a phospholipase A2 inhibitor, on the induction and maintenance of LTP in hippocampal slices. Brain Res 537: 49–53.PubMedCrossRefGoogle Scholar
  38. Morrison WR and Smith LM (1964) Preparation of fatty acid methyl esters and dimethylacetals from lipids with boron-trifluoride-methanol. J Lipid Res 5: 600–608.PubMedGoogle Scholar
  39. Moskowitz N, Schook W, Puszkin S (1984) Regulation of endogenous calciumdependent synaptic membrane phospholipase A2. Brain Res 290: 273–280.PubMedCrossRefGoogle Scholar
  40. Murphy SN and Miller RJ (1988) A glutamate receptor regulates Ca2+ mobilization in hippocampal neurons. Proc Natl Acad Sci USA 85: 8737–8741.PubMedCrossRefGoogle Scholar
  41. Piomelli D, Shapiro E, Feinmark SJ, Schwartz JH (1987) Metabolites of arachidonic acid in the nervous system of AplysiaPossible mediators of synaptic modulation. J Neurosci 7: 3675–3686.PubMedGoogle Scholar
  42. 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
  43. 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
  44. Sanfeliu C, Hunt A, Patel AJ (1990) Exposure to N-methyl-D-aspartate increases release of arachidonic acid in primary cultures of rat hippocampal neurons and not in astrocytes. Brain Res 526: 241–248.PubMedCrossRefGoogle Scholar
  45. 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
  46. Siesjo BK, Ingvar M, Westerberg E (1982) The influence of bicuculline-induced seizures on free fatty acid concentrations in cerebral cortex, hippocampus and cerebellum. J Neurochem 39: 796–802.PubMedCrossRefGoogle Scholar
  47. Sperk G, Lassman H, Baran H, Kish SJ, Seitelberger F, Hornykiewicz O (1983) Kainic acid induced seizures: Neurochemical and histopathological changes. Neuroscience 10: 1301–1315.PubMedCrossRefGoogle Scholar
  48. Straub H, Speckmann EJ, Bingmann D, Walden J (1990) Paroxysmal depolarization shifts induced by bicuculline in CA3 neurons of hippocampal slices: Suppression by the organic calcium antagonist verapamil. Neurosci Lett 111: 99–101.PubMedCrossRefGoogle Scholar
  49. Taniyama K, Saito N, Kose A, Matsuyama S, Nakayama S, Tanaka C (1990) Involvement of the gamma subtype of protein kinase C in GABA release from the cerebellum. Adv Second Messenger Phosphoprotein Res 24: 399–404.PubMedGoogle Scholar
  50. Volterra A and Siegelbaum SA (1988) Role of two different genuine nucleotide binding proteins in the antagonistic modulation of the S-type K+ channel by cAMP and arachidonic acid metabolites in Aplysiasensory neurons. Proc Natl Acad Sci USA 85: 7810–7814.PubMedCrossRefGoogle Scholar
  51. Williams JH, Errington ML, Lynch MA, Bliss TVP (1989) Arachidonic acid induces a long-term activity-dependent enhancement of synaptic transmission in the hippocampus. Nature 341: 739–742.PubMedCrossRefGoogle Scholar
  52. Zorumski CF and Yank J (1988) Non-competitive inhibition of GABA currents by phenothiazines in cultured chick spinal cord and rat hippocampal neurons. Neurosci Lett 92: 86–91.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1992

Authors and Affiliations

  • Dale L. Birkle
    • 1
  1. 1.Department of Pharmacology and ToxicologyWest Virginia UniversityMorgantownUSA

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