Inhibition of noradrenaline release by antibodies to B-50 (GAP-43).
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.
Dekker
L V
LV
Division of Molecular Neurobiology, University of Utrecht, The Netherlands.
De Graan
P N
PN
Oestreicher
A B
AB
Versteeg
D H
DH
Gispen
W H
WH
D000818:Animals; D001426:Bacterial Proteins; D002118:Calcium / Q000494:pharmacology; D002540:Cerebral Cortex / Q000502:physiology; D019922:GAP-43 Protein; D007074:Immunoglobulin G; D007700:Kinetics; D008565:Membrane Proteins / Q000276:immunology / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism*; D010539:Permeability; D010750:Phosphoproteins / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D013301:Streptolysins; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology
D001426:Bacterial Proteins; D019922:GAP-43 Protein; D007074:Immunoglobulin G; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D013301:Streptolysins; C025964:streptolysin O; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine