The neuropeptides are composed of two or more amino acids linked together by peptide bonds. Some 85 neuropeptides have been found, but their physiological roles are often unknown. It seems that evolution has selected the same chemical messengers for use in widely differing circumstances, and many of the neuropeptides had been previously identified in nonneural tissue where they function as hormones or paracrine agents. They generally retain the name they were given when first discovered in the nonneural tissue. The neuropeptides are formed differently from other neurotransmitters, which are synthesized in the axon terminals by very few enzyme-mediated steps.
The neuropeptides, in contrast, are derived from large precursor proteins, which in themselves have little, if any, inherent biological activity. The synthesis of these precursors is directed by mRNA and occurs on ribosomes, which exist only in the cell body and large dendrites of the neuron, often a considerable distance from axon terminals or varicosities where the peptides are released. In the cell body, the precursor protein is packaged into vesicles, which are then moved by axon transport into the terminals or varicosities where it is cleaved by specific peptidases. Many of the precursor proteins contain multiple peptides, which may be different or copies of one peptide. Neurons that release one or more of the peptide neurotransmitters are collectively called peptidergic. In many cases, neuropeptides are cosecreted with another type of neurotransmitter and act as neuromodulators.
The amount of peptide neurotransmitter released from vesicles at the synapse is significantly lower than the amount of nonpeptidergic neurotransmitter such as catecholamines. In addition, neuropeptides can diffuse away from the synapse and affect other neurons at some distance. The actions of these neuromodulators are longer-lasting (on the order of several hundred milliseconds) compared to other neurotransmitters. After release, these peptides interact with either ionotropic or metabotropic receptors. They are eventually broken down by peptidases located in the neuronal membrane. Certain neuropeptides, termed endogenous opioids-beta-endorphin, the dynorphins, and the enkephalins have attracted much interest because their receptors are the sites of action of opiate drugs such as morphine and codeine.