The Journal of Membrane Biology

, Volume 116, Issue 3, pp 261–272 | Cite as

Constant turnover of arachidonic acid and inhibition of a potassium current inAplysia giant neurons

  • Robert O. Carlson
  • Irwin B. Levitan
Articles

Summary

Steady-state currents at hyperpolarized membrane potentials were studied in the homologous giant neurons, LP1 and R2, ofAplysia using two-electrode voltage clamp. Nearly half of the steady-state current at voltages more hyperpolarized than −70 mV had characteristics similar to the inwardly rectifying potassium current (IR) described previously inAplysia neurons. The pharmacological agents 4-bromophenacylbromide, indomethacin, and the phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate were found to modulateIR.IR was stimulated with BPB and indomethacin and inhibited with TPA. These agents alteredIR by a mechanism independent ofcAMP, which can also modulateIR. The effects of these modulators are consistent with their actions on arachidonic acid (AA) metabolism inAplysia nervous system, suggesting AA may constitutively inhibitIR. When ganglia were perfused for 12 hr with medium containing BSA to absorb extracellular fatty acids,IR was increased nearly twofold. This increase was partially inhibited by addition of AA to the perfusion medium, and completely inhibited by pretreatment of ganglia with BPB. Although no direct effect of shortterm exposure to exogenous AA was observed, long term exposure to exogenous AA and several other unsaturated fatty acids was accompanied by a decrease inIR.

Key Words

arachidonic acid eicosanoids Aplysia inward rectifier phorbol ester potassium current protein kinase C 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Abou-Samra, A.B., Harwood, J.P., Catt, K.J., Aguilera, G. 1987. Mechanisms of action of CRF and other regulators of ACTH release in pituitary corticotrophs.Ann. N.Y. Acad. Sci. 512: 67–84PubMedGoogle Scholar
  2. 2.
    Adams, W.B., Levitan, I.B. 1982,. Intracellular injection of protein kinase inhibitor blocks the serotonin-induced increase in K+ conductance inAplysia neuron R15.Proc. Natl. Acad. Sci. USA 79: 3877–3880PubMedGoogle Scholar
  3. 3.
    Aguilera, G., Abou-Samra, A.B., Harwood, J.P., Catt, K.J. 1988. Corticotropin-releasing factor receptors: Characterization and actions in the anterior pituitary.Adv. Exp. Med. Biol. 245: 83–105Google Scholar
  4. 4.
    Beaumier, L., Faucher, N., Naccache, P.H. 1987. Arachidonic acid-induced release of calcium in permeabilized human neutrophils.FEBS Lett. 221: 289–292PubMedGoogle Scholar
  5. 5.
    Belardetti, F., Kandel, E.R., Siegelbaum, S.A. 1987. Neuronal inhibition by the peptide FMFRamide involves opening of S K+ channels.Nature (London) 325: 153–156Google Scholar
  6. 6.
    Benson, J.A., Levitan, I.B. 1983. Serotonin increases an anomalously rectifyingK + conductance inAplysia neuron R15.Proc. Natl. Acad. Sci. USA 80: 3522–3526PubMedGoogle Scholar
  7. 7.
    Bray, M.A., Ford-Hutchinson, A.W., Shipley, M.E., Smith, M.J.H. 1980. Calcium ionophore A23187 induces release of chemokinetic and aggregating factors from polymorphonuclear leukocytes.Br. J. Pharmacol. 71: 507–512PubMedGoogle Scholar
  8. 8.
    Camoratto, A.M. Grandison, L. 1985. Evidence supporting a correlatioin between arachidonic acid release and prolactin secretion from GH3 cells.Endocrinology 116: 1506–1513PubMedGoogle Scholar
  9. 9.
    Campbell, W.B., Falck, J.R., Okita, J.R., Johnson, A.R., Callahan, K.S. 1985. Synthesis of dihomoprostaglandins from adrenic acid (7,10,13,16-docosatetraenoic acid) by human endothelial cells.Biochim. Biophys. Acta 837: 67–76PubMedGoogle Scholar
  10. 10.
    Capdevila, J., Gil, L., Orellana, M., Marnett, L.J., Mason, J.I., Yadagiri, P., Falck, J.R. 1988. Inhibitors of cytochrome P-450-dependent arachidonic acid metabolism.Arch. Biochem. Biophys. 261: 257–263PubMedGoogle Scholar
  11. 11.
    Carlson, R.O., Levitan, I.B. 1990. Regulation of intracellular free arachidonic acid inAplysia nervous system.J. Membrane Biol. 116: 249–260Google Scholar
  12. 12.
    Cashman, J.R. 1989. 5,6-Epoxyeicosatrienoic acid stimulates growth hormone release in rat anterior pituitary cells.Life Sci. 44: 1387–1393PubMedGoogle Scholar
  13. 13.
    Cashman, J.R., Hanks, D., Weiner, R.I. 1987. Epoxy derivatives of arachidonic acid are potent stimulators of prolactin secretion.Neuroendocrinology 46: 246–251PubMedGoogle Scholar
  14. 14.
    Chan, K., Turk, J. 1987. Mechanism of arachidonic acid-induced Ca2+ mobilization from rat liver microsomes.Biochim. Biophys. Acta 928: 186–193PubMedGoogle Scholar
  15. 15.
    Chang, J.P., Graeter, J., Catt, K.J. 1986. Coordinate actions of arachidonic acid and protein kinase C in gonadotropin-releasing hormone-stimulated secretion of luteinizing hormone.Biochem. Biophys. Res. Commun. 134: 134–139PubMedGoogle Scholar
  16. 16.
    Chang, J.P., Graeter, J., Catt, K.J. 1987. Dynamic actions of arachidonic acid and protein kinase C in pituitary stimulation by gonadotropin-releasing hormone.Endocrinology 120: 1837–1845PubMedGoogle Scholar
  17. 17.
    Cheah, A.M. 1981. Effect of long chain unsaturated fatty acids on the calcium transport of sarcoplasmic reticulum.Biochim. Biophys. Acta 648: 113–119PubMedGoogle Scholar
  18. 18.
    Corey, E.J., Shih, C., Cashman, J.R. 1983. Docosahexaenoic acid is a strong inhibitor of prostaglandin but not leukotriene biosynthesis.Proc. Natl. Acad. Sci. USA 80: 3581–3584PubMedGoogle Scholar
  19. 19.
    Drummond, A., Benson, J., Levitan, I.B. 1980. Serotonin-induced hyperpolarization in an identifiedAplysia neuron is mediated by cyclic AMP.Proc. Natl. Acad. Sci. USA 77: 5013–5017PubMedGoogle Scholar
  20. 20.
    Flower, R.J. 1974. Drugs which inhibit prostaglandin biosynthesis.Pharmacol. Rev. 26: 33–67PubMedGoogle Scholar
  21. 21.
    Franson, R.C., Eisen, D., Jesse, R., Lanni, C. 1980. Inhibition of highly purified mammalian phospholipases A2 by nonsteroidal anti-inflammatory agents. Modulation by calcium ions.Biochem. J. 186: 633–636PubMedGoogle Scholar
  22. 22.
    Gunning, R. 1987. Increased numbers of ion channels promoted by an intracellular second messenger.Science 235: 80–82PubMedGoogle Scholar
  23. 23.
    Hagiwara, S., Takahashi, K. 1974. The anomalous rectification and cation selectivity of the membrane of starfish egg cell.J. Membrane Biol. 18: 61–80Google Scholar
  24. 24.
    Hong, S.L. 1988. The release of arachidonic acid from cellular lipids.Prog. Allergy 44: 99–139PubMedGoogle Scholar
  25. 25.
    Hong, S.L., Levine, L. 1976. Inhibition of arachidonic acid release from cells as the biochemical action of anti-inflammatory corticosteroids.Proc. Natl. Acad. Sci. USA 73: 1730–1734PubMedGoogle Scholar
  26. 26.
    Irvine, R.F. 1982. How is the level of free arachidnic acid controlled in mammalian cells?Biochem. J. 204: 3–16PubMedGoogle Scholar
  27. 27.
    Judd, A.M., Koike, K., MacLeod, R.M. 1985., GRF increases release of growth hormone and arachidonate from anterior pituitary cells.Am. J. Physiol. 248: E438-E442PubMedGoogle Scholar
  28. 28.
    Kiesel, L., Przylipiak, A., Emig, E., Rabe, T., Runnebaum, B. 1987. Stimulation of gonadotropin release by arachidonic acid and its lipoxygenase metabolites in superfused pituitary cells.Life Sci. 40: 847–851PubMedGoogle Scholar
  29. 29.
    Kiesel, L., Przylipiak, A., Rabe, T., Przylipiak, M., Runnebaum B. 1987. Arachidonic acid and its lipoxygenase metabolites stimulate prolactin release in superfused pituitary cells.Hum. Reprod. 2: 281–285PubMedGoogle Scholar
  30. 30.
    Kim, D., Clapham, D. E. 1989. Potassium channels in cardiac cells activated by arachidonic acid and phospholipids.Science 244: 1174–1176PubMedGoogle Scholar
  31. 31.
    Kim, D., Lewis, D.L., Graziadei, L., Neer, E.J., Bar-Sagi, D., Clapham, D. 1989. G-protein bg.-subunits activate the muscarinic K+-channel via phospholipase A2.Nature (London) 337: 557–560Google Scholar
  32. 32.
    Knepel, W., Schofl, C., Gotz, D.M. 1988. Arachidonic acid elevates cytosolic free calcium concentration in rat anterior pituitary cells.Naunyn Schmiedebergs Arch. Pharmacol. 338: 303–309PubMedGoogle Scholar
  33. 33.
    Kramer, R.H., Levitan, I.B. 1988. Calcium-dependent inactivation of a potassium current in theAplysia neuron R15.J. Neurosci. 8: 1796–1803PubMedGoogle Scholar
  34. 34.
    Kramer, R.M., Checani, G.C., Deykin, A., Pritzker, C.R., Deykin, D. 1986. Solubilization and properties of Ca2+-dependent human platelet phospholipase A2.Biochim. Biophys. Acta 878: 394–403PubMedGoogle Scholar
  35. 35.
    Kroner, E. E., Peskar, B.A., Fischer, H., Feber, E. 1981. Control of arachidonic acid accumulation in bone marrowderived macrophages by acyltransferases.J. Biol. Chem. 256: 3690–3697PubMedGoogle Scholar
  36. 36.
    Kurachi, Y., Ito, H., Sugimoto, T., Shimizu, T., Miki, I., Ui, M. 1989. Arachidonic acid metabolites as intracellular modulators of the G protein-gated cardiac K+ channel.Nature (London) 337: 555–557Google Scholar
  37. 37.
    Lagarde, M. 1988. Metabolism of fatty acids by platelets and the functions of various metabolites in mediating platelet function.Prog. Lipid Res. 27: 135–152PubMedGoogle Scholar
  38. 38.
    Leech, C.A., Stanfield, P.R. 1981. Inward rectification in frog skeletal muscle fibres and its dependence on membrane potential and external potassium.J. Physiol. (London) 319: 295–309Google Scholar
  39. 39.
    Levitan, E.S., Kramer, R.H., Levitan, I.B. 1987. Augmentation of bursting pacemaker activity by egg-laying hormone inAplysia neuron R15 is mediated by a cyclic AMP-dependent increase in Ca2+ and K+ currents.Proc. Natl. Acad. Sci. USA 84: 6307–6311PubMedGoogle Scholar
  40. 40.
    Luini, A.G., Axelrod, J. 1985. Inhibitors of the cytochrome P-450- enzymes block the secretagogue-induced release of corticotropin in mouse pituitary tumor cells.Proc. Natl. Acad. Sci. USA 82: 1012–1014PubMedGoogle Scholar
  41. 41.
    McGee, R., Jr., Sansom, M.S.P. Usherwood, P.N.R. 1988. Characterization of a delayed rectifier K+ channel in NG108-15 neuroblastomax glioma cells: Gating kinetics and the effects of enrichment of membrane phospholipids with arachidonic acid.J. Membrane Biol. 102: 21–34Google Scholar
  42. 42.
    Metz, S.A., Draznin, B., Sussman, K.E., Leitner, J.W. 1987. Unmasking of arachidonate-induced insulin release by removal of extracellular calcium Arachidonic acid mobilizes cellular calcium in rat islets of Langerhans.Biochem. Biophys. Res. Commun. 142: 251–258PubMedGoogle Scholar
  43. 43.
    Miyake, A., Nishizaki, T., Ikegami, H., Koike, K., Hirota, K., Tanizawa, O. 1988. Possible involvement of lipoxygenase pathway of arachidonate acid in rat pituitary hormone releasein vitro.J. Endocrinol. Invest. 11: 805–808PubMedGoogle Scholar
  44. 44.
    Neufeld, E.J., Bross, T.E., Majerus, P.W. 1984. A mutant HSDM1C1 fibrosarcoma line selected for defective eicosanoid precursor uptake lacks arachidonate-specific acyl-CoA synthetase.J. Biol. Chem. 259: 1986–1992PubMedGoogle Scholar
  45. 45.
    Nishizaki, T., Ikegami, H., Tasaka, K., Hirota, K., Miyake, A., Tanizawa, O. 1989. Mechanism of release of beta-endorphin from rat pituitary cells. Role of lipoxygenase products of arachidonic acid.Neuroendocrinology 49: 483–488PubMedGoogle Scholar
  46. 46.
    Ordway, R.W., Walsh, J.J., Singer, J.J. 1989. Arachidonic acid and other fatty acids directly activate potassium channels in smooth muscle cells.Science 244: 1176–1179PubMedGoogle Scholar
  47. 47.
    Piomelli, D., Shapiro, E., Feinmark, S.J. Schwartz, J.H. 1987. Metabolites of arachidonic acid in the nervous system ofAplysia: Possible mediators of synaptic modulation.J. Neurosci 7: 3675–3686PubMedGoogle Scholar
  48. 48.
    Piomelli, D., Volterra, A., Dale, N., Siegelbaum, S.A., Kandel, E.R., Schwartz, J.H., Belardetti, F. 1987. Lipoxygenase metabolites of arachidonic acid as second messengers for presynaptic inhibition ofAplysia sensory cells.Nature (London) 328: 38–43Google Scholar
  49. 49.
    Rittenhouse, S.S. 1980. Indomethacin-induced accumulation of diglyceride in activated human platelets. The role of diglyceride lipase.J. Biol. Chem. 255: 2259–2262PubMedGoogle Scholar
  50. 50.
    Rittenhouse-Simmons, S. 1981. Differential activation of platelet phospholipases by thrombin and ionophore A23187.J. Biol. Chem. 256: 4153–4155PubMedGoogle Scholar
  51. 51.
    Roberts, M.F., Deems, R.A., Mincey, T.C., Dennis, E.A. 1977. Chemical modification of the histidine residue in phospholipase A2 (Naja naja naja).J. Biol. Chem. 252: 2405–2411PubMedGoogle Scholar
  52. 52.
    Roman, I., Gmaj, P., Nowicka, C., Angielski, S. 1979. Regulation of Ca2+ efflux from kidney and liver mitochondria by unsaturated fatty acids and Na+ ions.Eur. J. Biochem. 102: 615–623PubMedGoogle Scholar
  53. 53.
    Setty, B.N., Stuart, M.J., Walenga, R.W. 1985. Formation of 11-HETE and 15-HETE in human umbilical arteries is catalyzed by cyclooxygenase.Biochim. Biophys. Acta 833: 484–494PubMedGoogle Scholar
  54. 54.
    Shuster, M.J., Camardo, J.S., Siegelbaum, S.A., Kandel, E.R. 1985. Cyclic AMP-dependent protein kinase closes the serotonin-sensitive K+ channels ofAplysia sensory neurones in cell-free patches.Nature (London) 313: 392–395Google Scholar
  55. 55.
    Siegel, M.I., McConnell, R.T., Porter, N.A., Selph, J.L., Truax, J.F., Vinegar, R., Cuatrecasas, P. 1980. Aspirin-like drugs inhibit arachidonic acid metablism via lipoxygenase and cyclooxygenase in rat neutrophils from carrageenan pleural exudates.Biochem. Biophys. Res. Commun. 92: 688–695PubMedGoogle Scholar
  56. 56.
    Siegelbaum, S.A., Camardo, J.S., Kandel, E.R. 1982. Serotonin and cyclic AMP close single K+ channels inAplysia sensory neurons.Nature (London).299: 413–417Google Scholar
  57. 57.
    Sircar, J.C., Schwender, C.F., Johnson, E.A. 1983. Soybean lipoxygenase inhibition by nonsteroidal antiinflammatory drugs.Prostaglandins 25: 393–396PubMedGoogle Scholar
  58. 58.
    Synder, G.D., Yadagiri, P., Falck, J.R. 1989. Effect of epoxyeicosatrienoic acids on growth hormone release from somatotrophs.Am. J. Physiol. 256: E221-E226PubMedGoogle Scholar
  59. 59.
    Spector, A.A., Yorek, M.A. 1985. Membrane lipid composition and cellular function.J. Lipid Res. 26: 1015–1035PubMedGoogle Scholar
  60. 60.
    Turk, J., Wolf, B.A., McDaniel, M.L. 1987. The role of phospholipid-derived mediators including arachidonic acid, its metabolites, and inositol-trisphosphate and of intracellular Ca2+ in glucose-induced insulin secretion by pancreatic islets.Prog. Lipid Res. 26: 125–181PubMedGoogle Scholar
  61. 61.
    Volwerk, J.J., Pieterson, W.A., de Haas, G.H. 1974. Histidine at the active site of phospholipase A2.Biochemistry 13: 1446–1454PubMedGoogle Scholar
  62. 62.
    Wolf, B.A., Turk, J., Sherman, W.R., McDaniel, M.L. 1986. Intracellular Ca2+ mobilization by arachidonic acid. Comparison with myo-inositol 1,4,5-trisphosphate in isolated pancreatic islets.J. Biol. Chem. 261: 3501–3511PubMedGoogle Scholar
  63. 63.
    Yammoto, S. 1989. Mammalian lipoxygenases: Molecular and catalytic properties.Prostaglandins Leukot. Essent. Fatty Acids 35: 219–229PubMedGoogle Scholar
  64. 64.
    Zeitler, P., Murphy, E., Handwerger, S. 1986. Arachidonic acid stimulates45calcium efflux and hPL release in isolated trophoblast cells.Life Sci. 38: 90–107Google Scholar

Copyright information

© Springer-Verlag New York Inc. 1990

Authors and Affiliations

  • Robert O. Carlson
    • 1
  • Irwin B. Levitan
    • 1
  1. 1.Graduate Department of BiochemistryBrandeis UniversityWaltham

Personalised recommendations