Neuropeptidemediated

Neuropeptide-mediated signaling refers to biological processes driven by neuropeptides, a diverse class of small peptide messengers synthesized in neurons and certain glial cells. Unlike classical neurotransmitters, many neuropeptides are co-released with amino acid transmitters and act at relatively low concentrations on receptors that may be distant or widely distributed, supporting volume transmission. They modulate circuit activity, neuroendocrine output, pain, feeding, social behavior, and immune responses.

Biogenesis and release: produced as larger propeptides, processed to active peptides in the secretory pathway, packaged into large dense-core vesicles, released in response to high-frequency activity, often from extrasynaptic sites, and can diffuse to nearby targets. Receptors are typically G protein–coupled, though some are ligand-gated ion channels; binding initiates second messenger cascades and gene regulation, leading to short-term effects and long-term plasticity.

Examples: substance P (pain and inflammation), neuropeptide Y (energy balance and stress), oxytocin and vasopressin (social behavior and water balance), enkephalins and endorphins (modulate nociception), calcitonin gene-related peptide (CGRP) (migraine pathophysiology).

Physiological and clinical relevance: neuropeptide signaling shapes sensory processing, stress responses, reproduction, and metabolism. Dysregulation is implicated in chronic pain, migraine, obesity, anxiety disorders, and neurodegenerative conditions. Therapeutics include receptor antagonists and peptides themselves, such as CGRP antagonists for migraine and NK1 receptor antagonists for substance P–related pain; however, peptide stability, delivery, and redundancy pose challenges.

Research considerations: study relies on immunoassays, mass spectrometry, receptor pharmacology, and genetic tools; advances in imaging and optogenetics are improving insights into neuropeptide action, including context-dependent signaling and network-level effects.