Tachykinin peptides

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.

= Neurotransmitters =

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.

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. 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, and it was shown that Substance P could promote wound healing of non-healing ulcers in humans.

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.

= 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.

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