Amino Acids

, Volume 46, Issue 7, pp 1727–1750

Involvement of substance P and the NK-1 receptor in human pathology

Original Article

DOI: 10.1007/s00726-014-1736-9

Cite this article as:
Muñoz, M. & Coveñas, R. Amino Acids (2014) 46: 1727. doi:10.1007/s00726-014-1736-9


The peptide substance P (SP) shows a widespread distribution in both the central and peripheral nervous systems, but it is also present in cells not belonging to the nervous system (immune cells, liver, lung, placenta, etc.). SP is located in all body fluids, such as blood, cerebrospinal fluid, breast milk, etc. i.e. it is ubiquitous in human body. After binding to the neurokinin-1 (NK-1) receptor, SP regulates many pathophysiological functions in the central nervous system, such as emotional behavior, stress, depression, anxiety, emesis, vomiting, migraine, alcohol addiction, seizures and neurodegeneration. SP has been also implicated in pain, inflammation, hepatitis, hepatotoxicity, cholestasis, pruritus, myocarditis, bronchiolitis, abortus, bacteria and viral infection (e.g., HIV infection) and it plays an important role in cancer (e.g., tumor cell proliferation, antiapoptotic effects in tumor cells, angiogenesis, migration of tumor cells for invasion, infiltration and metastasis). This means that the SP/NK-1 receptor system is involved in the molecular bases of many human pathologies. Thus, knowledge of this system is the key for a better understanding and hence a better management of many human diseases. In this review, we update the involvement of the SP/NK-1 receptor system in the physiopathology of the above-mentioned pathologies and we suggest valuable future therapeutic interventions involving the use of NK-1 receptor antagonists, particularly in the treatment of emesis, depression, cancer, neural degeneration, inflammatory bowel disease, viral infection and pruritus, in which that system is upregulated.


Substance P NK-1 receptor NK-1 receptor antagonists Molecular bases Human pathology 

Copyright information

© Springer-Verlag Wien 2014

Authors and Affiliations

  1. 1.Research Laboratory on Neuropeptides (IBIS)Virgen del Rocío University HospitalSevillaSpain
  2. 2.Unidad de Cuidados Intensivos PediátricosHospital Infantil Universitario Virgen del RocíoSevillaSpain
  3. 3.Laboratory of Neuroanatomy of the Peptidergic Systems (Lab. 14), Institute of Neurosciences of Castilla y León (INCYL)University of SalamancaSalamancaSpain

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