Neurokinin

Neurokinin refers to members of the tachykinin family of neuropeptides that function as neurotransmitters and neuromodulators in the central and peripheral nervous systems. The family includes substance P (SP), neurokinin A (NKA), neurokinin B (NKB), neurokinin C (NKC), and related peptides such as neuropeptide K (NPK) and neuropeptide gamma (NPG). These peptides are produced from precursor proteins encoded by the TAC1, TAC3, and TAC4 gene loci and are processed into active forms. They share a conserved C-terminal sequence typical of tachykinins.

Neurokinins exert their effects primarily through three G protein–coupled receptors, NK1, NK2, and NK3. Substance P has the highest affinity for NK1 receptors, neurokinin A preferentially binds NK2, and neurokinin B predominantly activates NK3. There is some cross-reactivity among receptor subtypes, contributing to a range of physiological responses. Receptor distribution is broad, with notable expression in the brain, spinal cord, and various peripheral tissues such as the gastrointestinal tract and vasculature.

Physiological roles of neurokinins include modulation of nociception and pain signaling, regulation of inflammation, vasodilation through release of other mediators like CGRP, and involvement in emesis, mood, and stress responses. In pathology, dysregulation of the tachykinergic system has been linked to migraine, chronic pain, inflammatory conditions, and mood disorders.

Clinical relevance centers on NK1 receptor antagonists, which are used to prevent chemotherapy-induced nausea and vomiting (for example, aprepitant, netupitant, and rolapitant). These agents underscore the therapeutic potential of targeting the neurokinin-NK receptor axis, while ongoing research explores additional indications and mechanisms of action.