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Receptors
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Biological and Pharmacological Aspects of the Neurokinin-1 Receptor
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Biological and Pharmacological Aspects of the Neurokinin-1 Receptor

A special issue of Receptors (ISSN 2813-2564).

Deadline for manuscript submissions: 30 June 2024 | Viewed by 9354

Special Issue Editors

Prof. Dr. Rafael Coveñas Rodríguez

E-Mail Website
Guest Editor
Laboratory of Neuroanatomy of the Peptidergic Systems, Institute of Neuroscience of Castilla and León (INCYL), University of Salamanca, c/ Pintor Fernando Gallego 1, 37007 Salamanca, Spain
Interests: cancer and anticancer peptides; substance P/neurokinin-1 receptor system; neurokinin-1 receptor antagonists
Special Issues, Collections and Topics in MDPI journals
Dr. Miguel Muñoz

E-Mail Website
Guest Editor
1. Pediatric Intensive Care United, Virgen del Rocio University Hospital, 41013 Seville, Spain
2. Research Laboratory on Neuropeptides (IBIS), Virgen del Rocio University Hospital, 41013 Seville, Spain
Interests: substance P; neurokinin-1 receptor; neurokinin-1 receptor antagonist; cancer; metastasis; angiogenesis; antitumor
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In recent years, knowledge regarding the involvement of peptides in human pathologies has attracted increasing interest. This has opened up new research lines and possibilities to explore new therapeutic strategies targeting specific molecular derangements. The undecapeptide substance P is a member of the tachykinin family of peptides derived from the TAC1 gene. The physiological/pathophysiological actions of substance P are mediated by the neurokinin-1, neurokinin-2, and neurokinin-3 receptors, although undecapeptide is the natural ligand with the highest affinity for the neurokinin-1 receptor which belongs to the G-protein-coupled receptor family. Substance P, after binding to the neurokinin-1 receptor, has been involved in many pathophysiological actions: vomiting, stress, depression, anxiety, alcohol addiction, pain, asthma, seizure, neurodegeneration, inflammatory diseases, migraine, viral and bacterial infection, cancer, hepatitis, hepatotoxicity, myocarditis, arthritis, platelet aggregation, epilepsy, colostasis, pruritus, and aggressive behavior. In these pathologies, the neurokinin-1 receptor/substance P system is upregulated, and hence, the neurokinin-1 receptor is an important therapeutic target because the use of neurokinin-1 receptor antagonists is a potential valuable therapeutic tool for the treatment of these pathologies. The knowledge of this system from basic molecular mechanisms to clinical aspects is crucial for a better understanding and management of many human diseases. Unfortunately, although in preclinical studies, the effective action of neurokinin-1 receptor antagonists has been shown, in general, this action has been ineffective in clinical trials. For this reason, it is crucial to know in depth the structure–function relationship of neurokinin-1 receptor/substance P for a rational design of new effective drugs. To increase the current knowledge of the role played by the neurokinin-1 receptor/substance P system in human diseases, this Special Issue will highlight all aspects regarding the involvement of this system in human pathologies, from basic molecular mechanisms to clinical results, and the promising use of neurokinin-1 receptor antagonists to treat human diseases. The aim of this Special Issue is to increase current knowledge of the biological/pharmacological aspects of the neurokinin-1 receptor to reach a profound knowledge of the neurokinin-1 receptor/substance P system that will allow an in-depth understanding and better handling of numerous human pathologies.

Prof. Dr. Rafael Coveñas Rodríguez
Dr. Miguel Muñoz
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Receptors is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (4 papers)

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Review

19 pages, 906 KiB  
Review
Evidence for the Involvement of the Tachykinin NK1 Receptor in Acute Inflammation of the Central Nervous System
by Renée J. Turner and Alan J. Nimmo
Receptors 2023, 2(4), 232-250; https://doi.org/10.3390/receptors2040016 - 15 Nov 2023
Cited by 1 | Viewed by 634
Abstract
Neuroinflammation is considered to be a significant component in a range of neuropathologies. Unfortunately, whilst its role is well recognised, the options for therapeutic intervention are limited. As such, there is a need to identify novel targets in order to increase treatment options. [...] Read more.
Neuroinflammation is considered to be a significant component in a range of neuropathologies. Unfortunately, whilst its role is well recognised, the options for therapeutic intervention are limited. As such, there is a need to identify novel targets in order to increase treatment options. Given its role as both a neurotransmitter and an immune modulator, substance P (SP) and its NK1 receptor (NK1R) have been widely studied as a potential therapeutic target. There is evidence that NK1R antagonists may exert beneficial effects in a range of conditions, including traumatic brain injury and stroke. Blocking the NK1R has been shown to reduce blood–brain barrier dysfunction, reduce cerebral oedema, and reduce the levels of pro-inflammatory cytokines. These actions are associated with improved survival and functional outcomes. The NK1R has also been shown to be involved in the inflammatory reaction to CNS infection, and hence antagonists may have some benefit in reducing infection-driven inflammation. However, the NK1R may also play a role in the host immune response to infection, and so here, the potential beneficial and detrimental effects need to be carefully balanced. The purpose of this review is to provide a summary of evidence for the involvement of the NK1R in acute CNS inflammation, particularly in the context of traumatic brain injury and stroke. Full article
(This article belongs to the Special Issue Biological and Pharmacological Aspects of the Neurokinin-1 Receptor)
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12 pages, 2080 KiB  
Review
The Role of Substance P and NK1 Receptors in Mild to Severe Traumatic Brain Injury: From CTE to ICP
by Robert Vink and Frances Corrigan
Receptors 2023, 2(4), 220-231; https://doi.org/10.3390/receptors2040015 - 11 Nov 2023
Viewed by 807
Abstract
Binding of substance P to the tachykinin NK1 receptor is involved in numerous physiological and pathophysiological processes ranging from modulation of sensory and motor function to inflammation, cancer, and brain injury, amongst others. NK1 antagonists therefore have enormous potential as a therapeutic intervention [...] Read more.
Binding of substance P to the tachykinin NK1 receptor is involved in numerous physiological and pathophysiological processes ranging from modulation of sensory and motor function to inflammation, cancer, and brain injury, amongst others. NK1 antagonists therefore have enormous potential as a therapeutic intervention in a wide variety of human disease states, albeit that the clinical potential is yet to be fully realised. In the current review, the role of substance P in the pathophysiology of traumatic brain injury (TBI) will be discussed, summarising both experimental and clinical observations in mild, moderate, and severe TBI. In addition, the potential for NK1 antagonists to be a valuable therapeutic intervention against chronic traumatic encephalopathy (CTE) after repeated concussive brain injury as well as raised intracranial pressure (ICP) following severe TBI will be addressed, highlighting the various pathophysiological processes that are attenuated by the intervention. Full article
(This article belongs to the Special Issue Biological and Pharmacological Aspects of the Neurokinin-1 Receptor)
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14 pages, 1512 KiB  
Review
The NK-1 Receptor Signaling: Distribution and Functional Relevance in the Eye
by Ibrahim Halil Demirsoy and Giulio Ferrari
Receptors 2022, 1(1), 98-111; https://doi.org/10.3390/receptors1010006 - 17 Nov 2022
Cited by 1 | Viewed by 3097
Abstract
Neurokinin-1 receptor (NK1R) signaling pathways play a crucial role in a number of biological processes in the eye. Specifically, in the ocular surface, their activity modulates epithelial integrity, inflammation, and generation of pain, while they have a role in visual processing in the [...] Read more.
Neurokinin-1 receptor (NK1R) signaling pathways play a crucial role in a number of biological processes in the eye. Specifically, in the ocular surface, their activity modulates epithelial integrity, inflammation, and generation of pain, while they have a role in visual processing in the retina. The NK1R is broadly expressed in the eye, in both ocular and non-ocular cells, such as leukocytes and neurons. In this review, we will discuss the roles of neurokinin-1 receptors and substance P (SP) in the physiopathology of eye disorders. Finally, we will review and highlight the therapeutic benefits of NK1R antagonists in the treatment of ocular diseases. Full article
(This article belongs to the Special Issue Biological and Pharmacological Aspects of the Neurokinin-1 Receptor)
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26 pages, 2121 KiB  
Review
The Neurokinin-1 Receptor: A Promising Antitumor Target
by Rafael Coveñas, Francisco D. Rodríguez and Miguel Muñoz
Receptors 2022, 1(1), 72-97; https://doi.org/10.3390/receptors1010005 - 07 Nov 2022
Cited by 4 | Viewed by 4008
Abstract
The important role played by the substance P (SP)/neurokinin-1 receptor (NK-1R) system in cancer is reviewed: this includes tumor cell proliferation and migration, anti-apoptotic mechanisms, and angiogenesis. SP, through the NK-1R, behaves as a universal mitogen in cancer cells. The NK-1R is overexpressed [...] Read more.
The important role played by the substance P (SP)/neurokinin-1 receptor (NK-1R) system in cancer is reviewed: this includes tumor cell proliferation and migration, anti-apoptotic mechanisms, and angiogenesis. SP, through the NK-1R, behaves as a universal mitogen in cancer cells. The NK-1R is overexpressed in tumor cells and, in addition, affects the viability of cancer cells. NK-1R antagonists counteract all the previous actions mediated by SP through NK-1R. In a concentration-dependent manner, these antagonists promote tumor cell death by apoptosis. Therefore, NK-1R is a potential and promising therapeutic target for cancer treatment by using NK-1R antagonists (e.g., aprepitant) alone or in combination therapy with chemotherapy or radiotherapy. Full article
(This article belongs to the Special Issue Biological and Pharmacological Aspects of the Neurokinin-1 Receptor)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: To be determined
Authors: Mark Kramer
Affiliation: Atlantic Wave Research Group LLC, Cherry Hill, NJ, USA.

Title: To be determined
Authors: Alan Nimmo
Affiliation: Centre for Molecular Therapeutics and College of Medicine and Dentistry, James Cook University, Cairns, QLD 4878, Australia

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