Substance P

In neuroscience, Substance P is a neuropeptide: a short-chain polypeptide that functions as a neurotransmitter and as a neuromodulator. It belongs to the tachykinin neuropeptide family.

It is an 11-amino acid polypeptide with the sequence: Arg Pro Lys Pro Gln Gln Phe Phe Gly Leu Met

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Receptor

The endogenous receptor for Substance P is neurokinin 1 receptor (NK1-receptor, NK1R). It belongs to the tachykinin receptor sub-family of GPCRs.

Functions

In the central nervous system, substance P has been associated in the regulation of mood disorders, anxiety, stress, reinforcement, neurogenesis, respiratory rhythm, neurotoxicity, nausea / emesis and pain.

Vomiting

The vomiting center in the brainstem contains high concentrations of substance P and its receptor, in addition to other neurotransmitters such as choline, histamine, dopamine, serotonin, and opioids. Their activation stimulates the vomiting reflex. Different emetic pathways exist, and substance P/NK1R appears to be within the final common pathway to regulate vomiting. ^[1]

Substance P antagonist (SPA) aprepitant is available in the market in the treatment of chemotherapy-induced nausea / emesis.

Pain

Substance P is involved in the transmission of pain impulses from peripheral receptors to the central nervous system. It has been theorized that it plays a part in fibromyalgia. Capsaicin has been shown to reduce the levels of Substance P probably by reducing the number of C-fibre nerves or causing these nerves to be more tolerant. Thus Capsaicin is clinically used as an analgesic and anti-inflammatory agent to relieve pain associated with arthritis and many types of neuralgia.

Stimulating cellular growth

Substance P has been shown to stimulate cellular growth in cell culture ^[2], and it was shown that Substance P could promote wound healing of non-healing ulcers in humans. ^[3] It has also been shown to reverse diabetes in mice. ^[4]

Vasodilation

It also has effects as a potent vasodilator. This is caused by the release of nitric oxide from the endothelium. Its release can cause hypotension.

Substance P in gastrointestinal infection

Entamoeba histolytica is a single-celled parasitic protozoan that infects the lower gastrointestinal tract of humans, producing symptoms of diarrhea, constipation, and abdominal pain.^[5][6] This protozoan was found to secrete serotonin^[7], as well as substance P and neurotensin.^[8]

Animals without Substance P

Naked mole rats lack Substance P and do not feel pain when painful stimuli are administered to the skin.^[9][10]

References

1. ^ Hornby PJ. Central neurocircuitry associated with emesis. Am J Med 2001;111:106S-12S
2. ^ Reid TW, Murphy C, Iwahashi C, Foster B, and Mannis M. Stimulation of epithelial cell growth by the neuropeptide substance P. J Cell Biochem 1993; 52:476-485
3. ^ Brown S, Lamberts D, Reid TW, Nishida T, Murphy C. Neurophilic and Anhidrotric Keratopathy Treated with Substance P and Insulinlike Growth Factor 1. Arch Ophthalmol 1997; 115:926-927
4. ^ Breakthrough sheds light on cause of diabetes - health - 15 December 2006 - New Scientist. Retrieved on 2007-05-08.
5. ^ Steinitz H (1979). "[Chronic recurrent intestinal amebiasis in Israel (author's transl)]" (in German). Leber, Magen, Darm 9 (4): 175-9. PMID 491812.
6. ^ Stark D, van Hal S, Marriott D, Ellis J, Harkness J (2007). "Irritable bowel syndrome: a review on the role of intestinal protozoa and the importance of their detection and diagnosis". Int. J. Parasitol. 37 (1): 11-20. doi:10.1016/j.ijpara.2006.09.009. PMID 17070814.
7. ^ McGowan K, Kane A, Asarkof N, et al (1983). "Entamoeba histolytica causes intestinal secretion: role of serotonin". Science 221 (4612): 762-4. PMID 6308760.
8. ^ McGowan K, Guerina V, Wicks J, Donowitz M (1985). "Secretory hormones of Entamoeba histolytica". Ciba Found. Symp. 112: 139-54. PMID 2861068.
9. ^ Park TJ, Comer C, Carol A, Lu Y, Hong HS, Rice FL (2003). "Somatosensory organization and behavior in naked mole-rats: II. Peripheral structures, innervation, and selective lack of neuropeptides associated with thermoregulation and pain". J Comp Neurol 465 (1): 104–20. doi:10.1002/cne.10824. PMID 12926019.
10. ^ Pepling, Rachel Sheremeta (January 7 2004). Ugly Ducklings. Chemical & Engineering News. Retrieved on 2007-08-14.