Tachykinin peptides
From Wikipedia, the free encyclopedia
Tachykinin peptides are one of the largest family of neuropeptides, found from amphibians to mammals.The tachykinin family is characterized by a common C-terminal sequence, Phe-X-Gly-Leu-Met-NH2, where X is either an Aromatic or an Aliphatic amino acid.
Contents |
[edit] Neurotransmitters
[edit] Substance P
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| Spacefilling model of substance P | |
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tachykinin, precursor 1
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| Identifiers | |
| Symbol(s) | TAC1 TAC2, NKNA |
| Entrez | 6863 |
| OMIM | 162320 |
| RefSeq | NM_003182 |
| UniProt | P20366 |
| Other data | |
| Locus | Chr. 7 q21-q22 |
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tachykinin receptor 1
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| Identifiers | |
| Symbol(s) | TACR1 TAC1R |
| Entrez | 6869 |
| OMIM | 162323 |
| RefSeq | NM_001058 |
| UniProt | P25103 |
| Other data | |
| Locus | Chr. 2 p13.1-p12 |
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.
Substance P is an 11-amino acid polypeptide with the sequence: Arg Pro Lys Pro Gln Gln Phe Phe Gly Leu Met NH2. 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.
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.
The endogenous receptor for Substance P is neurokinin 1 receptor (NK1-receptor, NK1R). It belongs to the tachykinin receptor sub-family of GPCRs.
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 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.
Substance P antagonist (SPA) aprepitant is available in the market in the treatment of chemotherapy-induced nausea / emesis.
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]
Chronic inflammation and pain are associated with a number of diseases, and it has been proposed that substance P, released from primary afferent nerve endings play a role in these conditions. Recent developments with substance P antagonists have demonstrated the importance of substance P in several models of disease that span from asthma to chronic bronchitis; from cystitis, inflammatory bowel disease to migraine; emesis, depression, pain and seizures. Advancements in the knowledge of the role of substance P, its agonists and antagonists could provide clinical solutions for a variety of chronic inflammatory conditions.
Naked Mole Rats lack Substance P and do not feel pain when painful stimuli are administered to the skin. Substance P receptors seem to play a big role in the rewarding effects of opiates, as mice lacking the substance p receptors don't get any reward from opiates like morphine.
[edit] Receptors
There are three known mammalian tachykinin receptors termed NK1, NK2 and NK3. All are members of the 7 transmembrane g protein-coupled family of receptors and induce the activation of phospholipase C, producing inositol triphosphate. NK1, NK2 and NK3 selectively bind to substance P, neurokinin A and neurokinin B, respectively. Whilst the receptors are not specific to any individual tachykinin, they do have differing affinity for the tachykinins: NK1: SP>NKA>NKB; NK2: NKA>NKB>SP; NK3: NKB>NKA>SP.
[edit] neurokinin 1 receptors
Antagonists of neurokinin-1 (NK(1)) receptors, through which substance P acts, have been proposed to belong to a new class of antidepressants
[edit] neurokinin 2 receptors
[edit] neurokinin 3 receptors
[edit] References
- ^ Hornby PJ. Central neurocircuitry associated with emesis. Am J Med 2001;111:106S-12S
- ^ 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
- ^ 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
