Epidermal growth factor-mediated inhibition of neurotransmitter glutamate release from rat forebrain synaptosomes

We investigated the possibility that receptor tyrosine kinases are involved in modulating neurotransmitter release from isolated nerve terminals. We examined the effects of epidermal growth factor on the release of neurotransmitter glutamate evoked from rat forebrain synaptosomes by KCl and 4-aminopyridine. We detected a significant inhibition of the Ca²⁺- dependent component of release. This effect appears to be mediated by a reduction in the depolarization-evoked increase in cytosolic free calcium levels, in the absence of significant effects on the plasma membrane potential. On depolarization, a Ca²⁺-dependent increase was observed in the phosphotyrosine content of bands at molecular masses of ~107 and ~40 kDa. The addition of epidermal growth factor before depolarization induced a significant phosphorylation of the growth factor receptor in the absence of detectable changes in the phosphotyrosine pattern of total synaptosomal proteins, suggesting that phosphorylation of a minor protein is responsible for the epidermal growth factor-mediated inhibition of glutamate release.