Tachykinin: recent developments and novel roles in health and disease

Abstract

Over 80 years has passed since the discovery of substance P (SP), and a variety of peptides of the tachykinin (TK) family have been found and investigated. SP, neurokinin A (NKA), and neurokinin B (NKB) are representative peptides in mammalian species. SP and NKA are major excitatory neurotransmitters in the peripheral nervous system, while NKB is primarily involved in the central nervous system (CNS). Moreover, TK peptides play roles not only as neurotransmitters but also as local factors and are involved in almost all aspects of the regulation of physiological functions and pathophysiological processes. The role of SP as a mediator of pain processing and inflammation in peripheral tissues in coordination with transient receptor potential channels is well established, while novel aspects of TKs in relation to hematopoiesis, venous thromboembolism, tendinopathy, and taste perception have been clarified. In the CNS, the NKB signaling system in the hypothalamus has been shown to play a crucial role in the regulation of gonadotropin hormone secretion and the onset of puberty, and molecular biological studies have elucidated novel prophylaxic activities of TKs against neurogenic movement disorders based on their molecular structure. This review provides an overview of the novel aspects of TKs reported around the world in the last 5 years, with particular focus on nociception, inflammation, hemopoiesis, gonadotropin secretion, and CNS diseases.

Serotonin and Neuropeptides in Blood From Episodic and Chronic Migraine and Cluster Headache Patients in Case‐Control and Case‐Crossover Settings: A Systematic Review and Meta‐Analysis

“…The major tachykinins (NKA, NKB, and SP) and CGRP are distributed throughout the peripheral and central nervous system 74,75 . Expression of signaling molecules, for example, in the trigeminovascular system 10,74,76,77 indicate a potential role in the migraine and CH pathophysiology. SP is expressed in the human trigeminal ganglia, 78 but clinical trials of SP blockers revealed no effect in acute migraine 79,80 .…”

“…Furthermore, no studies with focus on NKB for both primary headache disorders were identified. One explanation could be that NKB mainly seems to be involved in functions in the central nervous system, in contrast to SP and NKA which are considered key excitatory neurotransmitters in the peripheral nervous system 74,81 . Mapping signaling molecules (including others not investigated in this SR‐MA, for example, glutamate and gamma‐aminobutyric acid to investigate excitatory‐inhibitory balance) to the peripheral and central nervous system might, therefore, be beneficial prior to future selection of signaling molecules.…”

The role of vagal pathway andNK1andNK2receptors in cardiovascular and respiratory effects of neurokinin A

“…3,4 NKA and tachykinins receptors are involved in central and peripheral regulation of various physiological functions. 5,6 The mediating role of neurokinins in breathing has been disclosed by Bongianni et al, 2 who showed that exogenous agonists acting on receptors within the respiratory network control mainly the frequency of inspiratory bursts. Microinjection of NKA into the pre-BötC region in the rabbit evoked increases in respiratory frequency.…”

“…NKA acts as a full agonist on the three TK receptors although preferentially binds to the neurokinin NK 2 receptor . NKA and tachykinins receptors are involved in central and peripheral regulation of various physiological functions . The mediating role of neurokinins in breathing has been disclosed by Bongianni et al., who showed that exogenous agonists acting on receptors within the respiratory network control mainly the frequency of inspiratory bursts.…”

Hemokinin‐1 stimulates C‐C motif chemokine ligand 24 production in macrophages to enhance eosinophilic inflammation in nasal polyps

“…Tachykinins comprise a family of neuropeptides that are widely distributed in both central and peripheral nervous systems . Notably, the 3 classic tachykinins, SP, neurokinin A, and neurokinin B, have been implicated in the pathogenesis of airway diseases .…”