Figure 2. Neuropeptides broadly diffuse and act beyond the synapse.

Distinguishing features of fast synaptic transmission versus neuropeptide transmission are shown. Classical small molecule transmitters, such as glutamate, are stored in clear synaptic vesicles, while peptides are stored in dense core vesicles. The synaptic vesicles are rapidly recycled and refilled with neurotransmitter close to the synaptic cleft. Once released, neuropeptides are not taken back up into the neuron, so dense core vesicles are not regenerated at the synapse. Instead, dense core vesicles are replenished by axonal transport of new vesicles from the cell body. In addition, dense core vesicles are released from non-synaptic sites as indicated. Once released, classical neurotransmitters bind to ion channel receptors (ionotropic receptors), while nearly all neuropeptides bind to G-protein coupled receptors. A major feature of neuropeptides is their ability to act by volume transmission due to diffusion over a relatively large distance from the point of release to act on targets far from the synapse.