The Phospholipid Environment of Activated Synaptic Membrane Receptors May Provide Both Intracellularly and Retrogradely Acting Signals for the Regulation of Neuro(Muscular) Transmission

  • E. Heilbronn
  • L. Järlebark
Conference paper
Part of the Nato ASI Series book series (NATO ASI, volume 70)


The activation of two receptors of skeletal muscle and myotube in culture, the nicotinic acetylcholine receptor (nAChR) and the ATP-activated P2-purinergic receptor (P2R) resulted, in both cases, in increased intracellular levels of diacylglycerol (DAG). In the case of the receptor-ion channel macromolecule the intracellular DAG increases were seen after activation of nAChR by a cholinergic ligand and blocked by the nAChR inhibitors α-bungarotoxin or d-tubocurarine; they were dependent on the presence of external Ca2+, which points to the action of a phospholipase A2, present in the membrane and activated directly, probably via a G-protein, by nAChR. In the second case the P2R activates a G-protein-phospholipase C system which results in phosphoinositide turnover and a simultaneous increase in inositol phosphates and DAG, followed by intracellular Ca2+ movement and influx of Ca2+. It is discussed if DAG increases, when occurring close to the sarcolemma, might result in lipoxygenase products moving into the synapse and acting as “retrograde” signals. A preliminary experiment with arachidonic acid and a mouse phrenic nerve-diaphragm preparation was performed and showed no changes in MEPPs, while higher AA concentrations may have decreased the EPPs’ amplitudes.


Chromaffin Cell Nicotinic Acetylcholine Receptor Transmitter Release Lipoxygenase Product Bovine Adrenal Medulla 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adamo S, Zani BM, Nervi C, Senni MI, Molinaro M, Eusebi F (1985) Acetylcholine stimulate phosphatidylinositol turnover at nicotinic receptors of cultured rayotubes. FEBS Lett 190:161–164PubMedCrossRefGoogle Scholar
  2. Augustine GJ, Charlton MP, Smith SJ (1987) Calcium action in synaptic transmitter release. Annu Rev Neurosci 10:633–693PubMedCrossRefGoogle Scholar
  3. Berridge MJ (1984) Inositoltrisphosphate and diacylglycerol as second messengers. Biochem J 220:345–360PubMedGoogle Scholar
  4. Boksa P, Mykita S, Collier B (1988) Arachidonic acid inhibits choline uptake and depletes acetylcholine content in rat cerebral cortical synaptosomes. J Neurochem 50:1309–1318PubMedCrossRefGoogle Scholar
  5. Burnstock G, Buckley N (1985) The classification of receptor for adenosine and adenine nucleotides. In: Methods used in Adenosine Research, Methods in Pharmacology, vol 6, ed DM Paton. Plenum Press, New York, pp 193–212CrossRefGoogle Scholar
  6. Ehrengruber MU, Zahler P (1991) Inhibition of the nicotinic ion channel by arachidonic acid and other unsaturated fatty acids in chromaffin cells from bovine adrenal medulla. Chimia 45:45–49Google Scholar
  7. Eriksson H, Heilbronn E (1989) Extracellularly applied ATP alters the calcium flux through dihydropyridine-sensitive channels in cultured chick myotubes. Biochem Biophys Res Commun 159:878–885.PubMedCrossRefGoogle Scholar
  8. Eriksson H, Heilbronn H. The development of responses to extracellular ATP in cultured chick myotubes. Submitted.Google Scholar
  9. Huganir RL, Delcour AH, Greengard P, Hess GP (1986) Phosphorylation of the nicotinic acetylcholine receptor regulates its rate of desensitization. Nature 321:774–776PubMedCrossRefGoogle Scholar
  10. Huganir RL, Greengard P (1987) Regulation of receptor function by protein phosphorylation. Trends Pharmacol Sci 8:472–477CrossRefGoogle Scholar
  11. Huganir RL, Greengard P (1990) Regulation of neurotransmitter receptor desensitization by protein phosphorylation. Neuron 5:555–567PubMedCrossRefGoogle Scholar
  12. Heilbronn E, Järlebark L, Eriksson H. Membrane depolarization-induced release of lipids may participate in transmission regulation. J Neurochem, submitted.Google Scholar
  13. Häggblad J, Heilbronn E (1987) Externally applied adenosines’ triphosphate causes inositol triphosphate accumulation in cultured chick myotubes. Neurosci Lett 74:199–204PubMedCrossRefGoogle Scholar
  14. Häggblad J, Heilbronn E (1988) P2-purinoceptor stimulated phosphoinoitide turnover in chick myotubes. Calcium mobilization and the role of guanyl-nucleotide-binding proteins. FEBS Lett 235:133–136PubMedCrossRefGoogle Scholar
  15. Häggblad J, Eriksson H, Hedlund B, Heilbronn E (1987) Forskolin blocks carbachol-mediated ion-permeability of chick myotube nicotinic receptor and inhibits binding of 3H-phencyclidine to Torpedo microsac nicotinic receptors. Naunyn-Schmiedeberg’s Arch Pharmacol 336:381–386CrossRefGoogle Scholar
  16. Häggblad J, Eriksson H, Heilbronn E (1990) Cell surface ATP (P2y) purinoceptors trigger and modulate multiple calcium fluxes in skeletal muscle cells. In: Progress in Brain Research, Cholinergic Neurotransmisson: Functional and Clinical Aspects, vol 84, eds S-M Aguilonius, P-G Gillberg. Elsevier Science Publishers B V, pp 111–116CrossRefGoogle Scholar
  17. Irvine RF (1982) How is the level of free arachidonic acid controlled in mammalian cells? Biochem J 204:3–16PubMedGoogle Scholar
  18. Llinás R, McGuiness TL, Leonard CS, Sugimoro M, Greengard P (1985) Intraterminal injection of synapsin I or calcium/ calmodulin-dependent protein kinase II alters neurotransmitter release at the squid giant synapse. Proc Natl Acad Sei, USA 82:3035–3039CrossRefGoogle Scholar
  19. Lynch MA, Voss KL (1990) Arachidonic acid increases inositol phospholipid metabolism and glutamate release in synaptosomes prepared from hippocampal tissue. J Neurochem 55:215–221PubMedCrossRefGoogle Scholar
  20. Piomelli D, Greengard P (1990) Lipoxygenase metabolites of arachidonic acid in neuronal transmembrane signalling. Trends Pharmacol Sci 11:367–373PubMedCrossRefGoogle Scholar
  21. Piomelli D, Volterra A, Dale N, Siegelbaum SA, Kandel ER, Schwartz JH, Belardetti F (1987) Lipoxygenase metabolites of arachidonic acid as second messengers for presynaptic inhibition of Aplysia sensory cells. Nature 328:38–43PubMedCrossRefGoogle Scholar
  22. Piomelli D, Wang JKT, Sihra TS, Nairn AC, Czernik AJ, Greengard P (1989) Inhibition of Ca2+/calmodulin-dependent protein kinase II by arachidonic acid and its metabolites. Proc Natl Acad Sci USA 86:8550–8554PubMedCrossRefGoogle Scholar
  23. Ziboh VA, Isseroff RR, Pandey R (1984) Phospholipid metabolism in calcium-regulated differentiation in cultured murine keratinocytes. Biochem Biophys Res Commun 122:1234–1240PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

  • E. Heilbronn
    • 1
  • L. Järlebark
    • 1
  1. 1.Unit of Neurochemistry and NeurotoxicologyStockholm UniversityStockholmSweden

Personalised recommendations