UC Irvine

The calcium-stimulated release of several neurotransmitters has been studied in crude synaptosomal preparations following accumulation of various radioactively labeled neurotransmitters or their precursors. The high affinity uptake of D-aspartate, gamma-aminobutyric acid (GABA) and dopamine was not modulated in the presence of 5 mM of difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase (ODC). Depolarization-induced calcium influx caused release of labeled compounds. In the case of D-aspartate, this process was inhibited by DFMO. This major inhibition was completely reversed in the presence of 0.5 mM putrescine, the product of ODC-mediated catabolism of ornithine. This effect could not be shown for the depolarization-related release of dopamine, GABA or acetylcholine. In our preparation, a direct effect of the depolarizing medium upon levels of synaptosomal ODC could not be demonstrated, and the 50 mM K+-stimulated entry of 45Ca into the synaptosomal fraction was not inhibited by DFMO. These data suggest that polyamines are involved in the regulation of neurotransmitter release within certain classes of neurons.