The Neurokinin-1 receptor: structure dynamics and signaling

Rodríguez, Francisco D.; Coveñas, Rafael

doi:10.3390/RECEPTORS1010004

The Neurokinin-1 receptor: structure dynamics and signaling

Rodríguez, Francisco D. ¹
Coveñas, Rafael ²

1 Department of Biochemistry and Molecular Biology, Faculty of Chemical Sciences, University of Salamanca
2 Group GIR USAL: BMD (Bases Moleculares del Desarrollo), University of Salamanca
3 Laboratory of Neuroanatomy of the Peptidergic Systems, Institute of Neurosciences of Castilla and León (INCYL), University of Salamanca

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Revista:

Receptors

ISSN: 2813-2564

Año de publicación: 2022

Volumen: 1

Número: 1

Páginas: 54-71

Tipo: Artículo

DOI: 10.3390/RECEPTORS1010004 GOOGLE SCHOLAR Acceso abierto editor

Otras publicaciones en: Receptors

Resumen

Substance P (SP), the first isolated neuropeptide, belongs to the family of tachykinin peptides and is the natural ligand of neurokinin-1 receptors (NK-1R), also named SP receptors. The undecapeptide activates the receptor after specifically binding to the protein and triggers intracellular signals leading to different biochemical events and subsequent physiological responses. This study reviews the main architectural features of this receptor, its interaction with natural and synthetic ligands, and the functional conformational states adopted after interacting with ligands and effector G proteins. The analysis of the main intracellular signaling pathways turned on by the activation of NK-1 receptors reveals the participation of different proteins supporting metabolic changes and genetic and epigenetic regulations. Furthermore, the analysis of receptor occupancy and receptor downregulation and internalization represents a complex and estimable field for basic and clinical research focused on the role of SP in physiopathology. Profound knowledge of the structural dynamics of NK-1R may help develop and assay new selective synthetic non-peptide antagonists as potential therapeutic agents applied to various pathologies and symptoms.

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