Diffusion

In spite of the existence of transporters, the diffusion out of synapse may be significant for the inactivation of glutamate and GABA at synapses in the cerebral cortex. There is no high affinity reuptake for the peptides and though peptides may be internalized by neurons through receptormediated endocytosis and then degraded by the nonspecific peptidases, this is probably not a significant mechanism for their inactivation. Therefore the major route for terminating the synaptic action of peptides is by diffusion. Though, peptides are very much larger than the small classical transmitter molecules and there is important barriers for free diffusion out of the cleft. This means that peptides only clear slowly from a synapse that helps to elucidate why their actions can be so expanded.