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

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Abstract
PROTEIN kinase C (PKC) is believed to have a crucial role in synaptic transmitter release1–4 and long-term potentiation5–7. An important substrate of PKC in the brain is the neuron-specific presynaptically localized protein B-50 (also termed GAP-43, Fl, pp46 or P-57)8–11. B-50 has been implicated in the regulation of polyphosphoinositide metabolism12,13 and calmodulin binding14, and in the mechanisms of neurite outgrowth15,16, long-term potentiation17 and transmitter release18. 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.