Inhibition of noradrenaline release by antibodies to B-50 (GAP-43)

Nature. 1989 Nov 2;342(6245):74-6. doi: 10.1038/342074a0.


Protein kinase C (PKC) is believed to have a crucial role in synaptic transmitter release and long-term potentiation. An important substrate of PKC in the brain is the neuron-specific presynaptically localized protein B-50 (also termed GAP-43, F1, pp46 or P-57). B-50 has been implicated in the regulation of polyphosphoinositide metabolism and calmodulin binding, and in the mechanisms of neurite outgrowth, long-term potentiation and transmitter release. It is still unknown, however, whether B-50 (and/or its phosphorylation) is essential to any of these processes. Here we report the results of studies in which antibodies to B-50, which interfere with B-50 phosphorylation, were introduced into rat cortical synaptosomes that were permeabilized with streptolysin-O (SL-O). We found that the release of [3H]noradrenaline, induced by increasing the Ca2+ concentration in the buffer, is inhibited completely by the antibodies. These results provide the first demonstration of a causal relationship between the PKC substrate B-50 and the release of neurotransmitter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins
  • Calcium / pharmacology
  • Cerebral Cortex / physiology
  • GAP-43 Protein
  • Immunoglobulin G
  • Kinetics
  • Membrane Proteins / immunology
  • Membrane Proteins / physiology*
  • Nerve Tissue Proteins / immunology
  • Nerve Tissue Proteins / physiology*
  • Norepinephrine / metabolism*
  • Permeability
  • Phosphoproteins / physiology*
  • Potassium / pharmacology
  • Rats
  • Streptolysins
  • Synaptosomes / drug effects
  • Synaptosomes / metabolism*
  • Synaptosomes / physiology


  • Bacterial Proteins
  • GAP-43 Protein
  • Immunoglobulin G
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Phosphoproteins
  • Streptolysins
  • streptolysin O
  • Potassium
  • Calcium
  • Norepinephrine