Skip to main content
SpringerLink
Log in

Intracellular Requirements for Exocytotic Noradrenaline Release

  • Conference paper
Adrenergic System and Ventricular Arrhythmias in Myocardial Infarction

Abstract

Exocytosis, the process by which intracellular vesicles fuse with the inner surface of the plasma membrane, is thought to be the main mechanism underlying synaptic transmission at noradrenergic nerve terminals. A detailed study of the intracellular mechanisms involved has been hampered by the relative inaccesibility to the cytosol of markers that report intracellular chemical changes associated with secretion, or of solutes that clamp the chemical composition at the site of exocytosis. For this reason we have used not sympathetic nerve terminals as our experimental preparation, but instead the adrenal medullary (chromaffin) cell [1]. Although the medulla is part of the endocrine system, the cells are derived embryologically from neural crest tissue and retain the neuronal properties of excitable tissue, that is they exhibit sodium dependent action potentials and have voltage sensitive calcium channels [2]. One marked difference between an adrenal medullary cell and a sympathetic nerve terminal is the rate of secretion of transmitter. All the evidence suggests that noradrenaline is secreted form nerve terminals within milliseconds of the arrival of an action potential, whereas secretion from the adrena medullary cell proceeds at a much slower rate [3]. Apart from this difference the adrenal medullary cell serves as an excellent model of a sympathetic neurone in which to study the mechanism of catecholamine secretion, and this short article reviews the experimental approaches we have used here at King’s College, the results and conclusions reached, and the direction we will be taking in the future.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Knight DE, Baker PF (1983) Stimulus secretion coupling in isolated bovine adrenal medullary cells. Q J Exp Physiol 68:123–143.

    PubMed  CAS  Google Scholar 

  2. Fenwick EM, Marty A, Neher E (1982) Sodium & calcium channels in bovine chromaffin cells. J Physiol Lond 331:599–635.

    PubMed  CAS  Google Scholar 

  3. Knight DE, Sugden D, Baker PF (1988) The evidence implicating protein kinase C in exocytosis from electropermeabilised bovine chromaffin cells. J Memb Biol 104:21–34.

    Article  CAS  Google Scholar 

  4. Douglas WW (1968) Stimulus secretion coupling: the concept and clues from chromaffin and other cells. Br J Pharmacol 34:451–474.

    PubMed  CAS  Google Scholar 

  5. Garcia AG, Sala F, Reig JA, Viniegra S, Frias J, Fronteriz R, Gandia L (1984) Dihydropyridine BAY-K-8644 activates chromaffin cell calcium channels. Nature 309:69–71.

    Article  PubMed  CAS  Google Scholar 

  6. Tsien RY (1981) A non disruptive technique for loading Ca buffers and indicators into cells. Nature 290:527–528.

    Article  PubMed  CAS  Google Scholar 

  7. Llinas RJ, Blinks R, Nicholson C (1972) Calcium transients in presynaptic terminal of squid giant axon. Detection with aequorin. Science 176:1127–1129.

    Article  PubMed  CAS  Google Scholar 

  8. Knight DE, Kesteven NT (1983) Evoked transient intracellular free Ca2+ changes and secretion in isolated bovine adrenal medullary cells. Proc R Soc Lond [Biol] 218:177–199.

    Article  CAS  Google Scholar 

  9. Burgoyne RD (1984) The relationship between secretion and intracellular free calcium in bovine adrenal chromaffin cells. Biosci Rep 7:605–611.

    Article  Google Scholar 

  10. Cobbold PE, Cheek TR, Cuthbertson KS, Burgoyne RD (1987) Calcium transients in single adrenal chromaffin cells detected with aequorin. FEBS Lett 211:44–48.

    Article  PubMed  CAS  Google Scholar 

  11. Artalejo CR, Garcia AG, Aunis D (1987) Chromaffin cell calcium channel kinetics measured isotopically through fast calcium, strontium, and barium fluxes. J Biol Chem 262:915–926.

    PubMed  CAS  Google Scholar 

  12. Grynkiewicz G, Poenie M, Tsien RY (1985) A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 260:3440–3450.

    PubMed  CAS  Google Scholar 

  13. Baker PF, Meeves H, Ridgway EB (1973) Calcium entry in response to maintained depolarisation of squid axons. J Physiol (Lond) 231:527–548.

    CAS  Google Scholar 

  14. Hess P, Lansman JB, Tsien RW (1984) Different modes of Ca channel gating behaviour favoured by dihydropyridine Ca agonists and antagonists. Nature 311:538–544.

    Article  PubMed  CAS  Google Scholar 

  15. Nowycky MC, Fox AP, Tsien RW (1985) Three types of neuronal calcium channel with different agonist activity. Nature 316:440–443.

    Article  PubMed  CAS  Google Scholar 

  16. Reuter H (1983) Calcium channel modulation by neurotransmitters, enzymes and drugs. Nature 301:569–574.

    Article  PubMed  CAS  Google Scholar 

  17. Baker PF, Knight DE (1978) Calcium dependent exocytosis in bovine adrenal medullary cells with leaky plasma membranes. Nature 276:620–622.

    Article  PubMed  CAS  Google Scholar 

  18. Knight DE, Baker PF (1982) Calcium dependence of catecholamine release from bovine adrenal medullary cells after exposure to intense electric fields. J Membr Biol 68:107–140.

    Article  PubMed  CAS  Google Scholar 

  19. Knight DE, Scrutton MC (1986) Gaining access to the cytosol: the technique and some applications. Biochem J 234:497–506.

    PubMed  CAS  Google Scholar 

  20. Gomperts BD, Fernandez JM (1985) Techniques for membrane permeabilisation. Trends Biochem Sci 10:414–417.

    Article  Google Scholar 

  21. Knight DE, Baker PF (1983) The phorbol ester TPA increases the affinity of exocytosis for CA in leaky adrenal medullary cells. FEBS Lett 160:98–100.

    Article  PubMed  CAS  Google Scholar 

  22. Brocklehurst KW, Pollard BP (1985) Enhancement of Ca2+ induced catecholamine release by the phorbol ester TPA in digitonin-permeabilised cultured bovine adrenal chromaffin cells. FEBS Lett 183:107–110.

    Article  PubMed  CAS  Google Scholar 

  23. TerBush DR, Holz RW (1986) Effects of phorbol esters, diglyceride, and cholinergic agonists on the subcellular distribution of protein kinase C in intact or digitonin-permeabilised adrenal chromaffin cells. J Biol Chem 261:17099–17106.

    PubMed  CAS  Google Scholar 

  24. Kenigsberg RL, Trifaro J-M (1985) Microinjection of calmodulin antibodies into cultured chromaffin cells blocks catecholamine release in response to stimulation. Neuroscience 14:335–347.

    Article  PubMed  CAS  Google Scholar 

  25. Creutz CE, Pazoles CJ, Pollard HB (1978) Identification & purification of an adrenal medullary protein (synexin) that causes the calcium-dependent aggregation of isolated chromaffin granules. J Biol Chem 253:2858–2866.

    PubMed  CAS  Google Scholar 

  26. Pollard HB, Scott JH, Creutz CE (1983) Inhibition of synexin activity & exocytosis from chromaffin cells by phenothiazine drugs. Biochem Biophys Res Commun 113:908–915.

    Article  PubMed  CAS  Google Scholar 

  27. Drust DS, Creutz CE (1983) Aggregation of chromaffin granules by calpactin at micromolar levels of calcium. Nature 331:88–91.

    Article  Google Scholar 

  28. Creutz CE, Zaks WJ, Hamman HC, Crane S, Martin WH, Gould KL, Oddie KM, Parsons SJ (1987) Identification of chromaffin granule-binding proteins. Relationship of the chromobindins to calelectrin, synhibin and the tyrosine kinase substrates p35 and p36. J Biol Chem 262:1860–1868.

    PubMed  CAS  Google Scholar 

  29. Sudhhof TCE, Ebbecke M, Walker JH, Fritsche U, Boustead C (1984) Isolation of mammalian calelectrins: a new class of ubiquitous Ca2+-regulated proteins. Biochemistry 23:1103–1109.

    Article  Google Scholar 

  30. Sobue K, Tanaka T, Kand K, Ashumo N, Kakiuchi S (1985) Purification and characterisation of caldesmon. PNAS 82:5025–5029.

    Article  PubMed  CAS  Google Scholar 

  31. White J, Kielan M, Helenius A (1983) Membrane fusion proteins of enveloped animal viruses. Q Rev Biophys 16:151–196.

    Article  PubMed  CAS  Google Scholar 

  32. Nishizuka Y (1984) The role of protein kinase C in cell surface signal transduction and tumor promotion. Nature 308:693–698.

    Article  PubMed  CAS  Google Scholar 

  33. Castagna M, Takai Y, Kaibuchi K, Sano K, Kikkawa U, Nishizuka Y (1982) Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem 257:7847–7851.

    PubMed  CAS  Google Scholar 

  34. Phillips JH, Burridge KE, Wilson SP, Kirshner N (1983) Visualisation of the exocytosis and endocytosis in secretory cycle in cultured adrenal chromaffin cells. J Cell Biol 97:1906–1917.

    Article  PubMed  CAS  Google Scholar 

  35. von Grafensein H, Roberts CS, Baker PF (1986) The kinetics of the exocytosis endocytosis secretory cycle in bovine adrenal medullary cells. J Cell Biol 103:2343–2352.

    Article  Google Scholar 

  36. Baker PF, Knight DE (1981) Calcium control of exocytosis & endocytosis in bovine adrenal medullary cells. Philos Trans R Soc Lond [Biol] 296:83–103.

    Article  CAS  Google Scholar 

  37. Baker PF, Knight DE, Roberts CS (1982) Morphology of bovine adrenal medullary cells after exposure to brief intense electric fields. J Physiol (Lond) 326:6–7P.

    Google Scholar 

  38. von Grafenstein H (1988) Endocytosis following triggered exocytosis in permeabilised bovine adrenal medullary cells is calcium-independent and blocked by non-hydrolysable analogues of ATP. J Physiol (Lond) 403:54P.

    Google Scholar 

  39. Perrin D, Langley OK, Aunis D (1987) Anti-α-fodrin inhibits secretion from permeabilised chromaffin cells. Nature 326:498–501.

    Article  PubMed  CAS  Google Scholar 

  40. Burgoyne RD, Geisow MJ, Barron J (1982) Dissection of stages in exocytosis in the adrenal chromaffin cell with use of trifluoperazine. Proc R Soc Lond [Biol] 216:111–115.

    Article  CAS  Google Scholar 

  41. Cheek TR, Burgyone RD (1986) Nicotine-evoked disassembly of cortical actin filaments in adrenal chromaffin cells. FEBS Lett 207:110–114.

    Article  PubMed  CAS  Google Scholar 

  42. Burgyone RD, Cheek TR (1987) Reorganisation of peripheral actin filaments as a prelude to exocytosis. Biosci Rep 7:281–288.

    Article  Google Scholar 

  43. Vilmart-Seuwen J, Kersken H, Sturzl R, Plattner H (1986) ATP keeps exocytosis sites in a primed state, but is not required for membrane fusion: an analysis with paramecium cells in vivo and in vitro. J Cell Biol 103:1279–1288.

    Article  PubMed  CAS  Google Scholar 

  44. Navonne F, Greengard P, DeCamillo P (1984) Synapsin 1 in nerve terminals: selective association with small synaptic vesicles. Science 226:1209–1211.

    Article  Google Scholar 

  45. Llinas R, McGuiness T, Leonard D, Sugimori M, Geengard P (1985) Intraterminal injection of synapsin 1 or calcium/calmodulin dependent protein kinase 11 alters the neutrotransmitter release at the squid giant synapse. Proc Nat Acad Sci USA 83:3035–3039.

    Article  Google Scholar 

  46. Zeiseniss E, Plattner M (1985) Synchronous exocytosis in paramecium cells involves very rapid reversible dephosphorylation of a 65KD phosphoprotein in exocytosis — component strains. J Cell Biol 101:2028–2035.

    Article  Google Scholar 

  47. Lumpert CJ, Kersken H, Gras U, Plattner H (1987) Screening of enzymatic mechanisms possibly involved in membrane fusion during exocytosis in paramecium cells. Cell Biol Int Rep 11:405–414.

    Article  PubMed  CAS  Google Scholar 

  48. Niggli V, Knight DE, Baker PF, Vigny A, Henry J-P (1984) Tyrosine hydroxylase in leaky adrenal medullary cells: evidence for in situ phosphorylation by separate Ca2+ and cAMP dependent systems. J Neurochem 43:646–658.

    Article  PubMed  CAS  Google Scholar 

  49. Lee SA, Holz RW (1986) Protein phosphorylation and secretion in digitonin-permeabilised adrenal chromaffin cells. J Biol Chem 261:17089–17098.

    PubMed  CAS  Google Scholar 

  50. Salama G, Johnson RG, Scarpa A (1980) Spectrophotometric measurements of transmem-brane potential and pH gradients in chromaffin granules. J Gen Physiol 75:109–140.

    Article  PubMed  CAS  Google Scholar 

  51. Pollard HB, Pazoles CJ, Creutz CE et al. (1977) A role for anion transport in the regulation and release from chromaffin granules and exocytosis. J Supramol Struct 7:277–285.

    Article  PubMed  CAS  Google Scholar 

  52. Knight DE, Baker PF (1985) The chromaffin granule proton pump and CA dependent exocytosis in bovine adrenal medullary cells. J Memb Biol 83:147–156.

    Article  CAS  Google Scholar 

  53. Knight DE, Baker PF (1985) Guanine nucleotides and CA-dependent exocytosis: studies on two adrenal preparations. FEBS Lett 189:345–349.

    Article  PubMed  CAS  Google Scholar 

  54. Barrowman MM, Cockcroft S, Gomperts BD (1986) Two roles for guanine nucleotides in the stimulus secretion sequence of neutrophils. Nature 319:504–507.

    Article  PubMed  CAS  Google Scholar 

  55. Bittner MA, Holz RW, Neubig RR (1986) Guanine nucleotide effects on catecholamine secretion form digitonin-permeabilised adrenal chromaffin cells. J Biol Chem 261:10182–10188.

    PubMed  CAS  Google Scholar 

  56. Lundberg JM, Terenius L, Hokfelt T, Goldstein M (1983) High levels of neuropeptide Y in peripheral noradrenergic neurons in various mammals including man. Neurosci Lett 42:167.

    Article  PubMed  CAS  Google Scholar 

  57. Edvinsson L, Ekblad E, Hakanson R, Wahlestedt C (1984) Neuropeptide Y potentiates the effect of various vasoconstrictor agents on rabbit blood vessels. Br J Pharmacol 83:519.

    PubMed  CAS  Google Scholar 

  58. Bartifai T (1985) Presynaptic aspects of the coexistence of classical neurotransmitters and Peptides. Trends Pharmacol Sci 6:331–334.

    Article  Google Scholar 

  59. Knight DE, Niggli V, Scrutton MC (1984) Thrombin and activators of protein kinase C modulate secretory responses of permeabilised human platelets induced by Ca2+. Eur J Biochem 143:437–446.

    Article  PubMed  CAS  Google Scholar 

  60. Davey J (1987) A cell-free analysis of the endocytotic pathway. Biosci Rep 7:299–306.

    Article  PubMed  CAS  Google Scholar 

  61. Crabb JH, Modern PA, Jackson RC (1987) In vitro reconstitution of exocytosis from sea urchin egg plasma membrane and isolated cortical vesicles. Biosci Rep 7:399–410.

    Article  PubMed  CAS  Google Scholar 

  62. Sarafian T, Aunis D, Bader M-F (1987) Loss of protein from digitonin-permeabilised adrenal chromaffin cells essential for exocytosis. J Biol Chem 262:16671–16676.

    PubMed  CAS  Google Scholar 

  63. Knight DE, Tonge DA, Baker PF (1985) Inhibition of exocytosis in bovine adrenal medullary cells by botulinum toxin type D. Nature 317:719–721.

    Article  PubMed  CAS  Google Scholar 

  64. Penner R, Neher E, Dreyer F (1986) Intracellularly injected tetanus toxin fragment B inhibit exocytosis in bovine adrenal chromaffin cells. Nature 324:76–78.

    Article  PubMed  CAS  Google Scholar 

  65. Knight DE (1986) Botulinum toxin types A, B, and D inhibit catecholamine secretion from bovine adrenal medullary cells. FEBS Lett 207:222–226.

    Article  PubMed  CAS  Google Scholar 

  66. Ohashi Y, Narumiya S (1987) ADP-ribosylation of a Mr 21000 membrane protein by type D botulinum toxin. J Biol Chem 262:1430–1433.

    PubMed  CAS  Google Scholar 

  67. Adam-Vizi V, Rosener S, Aktories K, Knight DE (1988) Botulinum toxin induced ADP-ribosylation and inhibiton of exocytosis are unrelated events. FEBS Lett 104:277–280.

    Article  Google Scholar 

  68. Knight DE (1987) Calcium and diacylglycerol control of secretion. Biosci Rep 7:355–368.

    Article  PubMed  CAS  Google Scholar 

  69. Grynkiewicz G, Poenie M, Tsien RY (1985) A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 260:3440–3450.

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. D. E. Knight
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. Von Grafenstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. J. Maconochie
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Abteilung für Innere Medizin III, Kardiologie Medizinische Universitätsklinik, Bergheimer Straße 58, 6900, Heidelberg 1, Germany

    J. Brachmann  & A. Schömig  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1989 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Knight, D.E., Von Grafenstein, H., Maconochie, D.J. (1989). Intracellular Requirements for Exocytotic Noradrenaline Release. In: Brachmann, J., Schömig, A. (eds) Adrenergic System and Ventricular Arrhythmias in Myocardial Infarction. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-74317-7_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-74317-7_1

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-74319-1

  • Online ISBN: 978-3-642-74317-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation