Neuropeptides

Neuropeptides are endogenous peptide transmitters that regulate neuronal communication and hormonal signaling. They are typically short chains of amino acids derived from larger precursor proteins (prepropeptides) that are synthesized in the neuron's cell body, processed in the secretory pathway, and packaged into dense-core vesicles for transport to nerve terminals. They are released in response to neuronal activity and often diffuse to act on receptors located at some distance from the release site, producing effects that last from seconds to hours.

Most neuropeptides act as neuromodulators or neurohormones rather than fast, point-to-point transmitters. They frequently co-release with classical neurotransmitters such as glutamate or GABA and modulate synaptic strength, neuronal excitability, or network dynamics through G protein–coupled receptors, although some receptors can be ion channels or other types. Signaling typically involves second messengers such as cyclic AMP, IP3/DAG, or intracellular Ca2+ changes, leading to long-lasting changes in neuronal function and gene expression.

Examples of neuropeptides include substance P (pain signaling), enkephalins and other opioid-related peptides (pain and reward modulation), neuropeptide Y (feeding and energy balance), oxytocin and vasopressin (social behavior, water homeostasis), corticotropin-releasing factor (stress response), vasoactive intestinal peptide, cholecystokinin, neurotensin, and calcitonin gene-related peptide. Many of these peptides have diverse roles across the central nervous system and peripheral tissues.

Clinical relevance includes the use of peptide drugs and analogs in treating disorders such as migraine, diabetes-related conditions, and certain endocrine or psychiatric disorders, though central delivery remains challenging due to stability and blood–brain barrier considerations.