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

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Abstract

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.

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Acknowledgments

The authors thank N. Skinner (University of Salamanca, Spain) for stylistic revision of the English text. The technical assistance of Dr. Miguel E. Muñoz (Virgen del Rocío University Hospital, Sevilla, Spain) and Mr. Javier Muñoz (University of Sevilla, Spain) is gratefully acknowledged.

Conflict of interest

USPTO Application no. 20090012086 “Use of non-peptide NK-1 receptor antagonists for the production of apoptosis in tumor cells” (Miguel Muñoz).

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  1. Research Laboratory on Neuropeptides (IBIS), Virgen del Rocío University Hospital, Sevilla, Spain

    Miguel Muñoz

  2. Unidad de Cuidados Intensivos Pediátricos, Hospital Infantil Universitario Virgen del Rocío, Av. Manuel Siurot s/n, 41013, Sevilla, Spain

    Miguel Muñoz

  3. Laboratory of Neuroanatomy of the Peptidergic Systems (Lab. 14), Institute of Neurosciences of Castilla y León (INCYL), University of Salamanca, Salamanca, Spain

    Rafael Coveñas

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  1. Miguel Muñoz
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Muñoz, M., Coveñas, R. Involvement of substance P and the NK-1 receptor in human pathology. Amino Acids 46, 1727–1750 (2014). https://doi.org/10.1007/s00726-014-1736-9

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