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. It has also been shown to reverse diabetes in mice.

Naked Mole Rats lack Substance P and do not feel pain when painful stimuli are administered to the skin.