Neuropeptide

Neuropeptides are chemical messengers made up of small chains of amino acids that are synthesized and released by neurons.

Neuropeptides typically bind to G protein-coupled receptors (GPCRs) to modulate neural activity and other tissues like the gut, muscles, and heart.

Peptides are packaged into dense core vesicles, where further cleaving and processing, such as C-terminal amidation, can occur.

Dense core vesicles are transported throughout the neuron and can release peptides at the synaptic cleft, cell body, and along the axon.

[4] Neuropeptides utilize volume transmission and are not reuptaken quickly, allowing diffusion across broad areas (nm to mm) to reach targets.

Almost all neuropeptides bind to G protein-coupled receptors (GPCRs), inducing second messenger cascades to modulate neural activity on long time-scales.

[12] Due to their modulatory and diffusive nature, neuropeptides can act on multiple time and spatial scales.

At low frequency activation, only glutamate is released, yielding fast and rapid excitation of the muscle.

At high frequency activation however, dense core vesicles release proctolin, inducing prolonged contractions.

[21][22] Genome sequencing reveals evidence of neuropeptide genes in Cnidaria, Ctenophora, and Placozoa, some of oldest living animals with nervous systems or neural-like tissues.

[26] Additionally, Ctenophore and Placozoa neural signaling is entirely peptidergic and lacks the major amine neurotransmitters such as acetylcholine, dopamine, and serotonin.

In the early 1900s, chemical messengers were crudely extracted from whole animal brains and tissues and studied for their physiological effects.

In 1931, von Euler and Gaddum, used a similar method to try and isolate acetylcholine but instead discovered a peptide substance that induced physiological changes including muscle contractions and depressed blood pressure.