Substance P TFA

Substance P is tachykinin neuropeptide that selectively binds to neurokinin 1 (NK₁) receptors (K_is = 0.14 and 300 nM for NK₁ and NK₃, respectively) and has diverse biological activities.^1,2 It is an endogenous peptide expressed in the central and peripheral nervous systems, including the enteric nervous system and in immune cells.² Substance P is released with other neurotransmitters in the dorsal horn of the spinal cord following noxious peripheral stimulation and induces pain through NK₁ receptors.³ The NK₁ receptor is internalized following substance P binding, and in a rat hindpaw model of inflammation it is internalized in a greater number of spinal cord neurons following a mechanical or non-noxious stimuli, indicating a role for substance P in inflammation and hyperalgesia.⁴ Substance P is also involved in depression, anxiety, seizures, and emesis among other functions.²

1.Gether, U., Johansen, T.E., Snider, R.M., et al.Different binding epitopes on the NK1 receptor for substance P and non-peptide antagonistNature362(6418)345-348(1993) 2.Mu?oz, M., and Cove?as, R.Involvement of substance P and the NK-1 receptor in human pathologyAmino Acids46(7)1727-1750(2014) 3.Mantyh, P.H.Neurobiology of substance P and the NK1 receptorJ. Clin. Psychiatry63(Suppl 11)6-10(2002) 4.Abbadie, C., Trafton, J., Mantyh, P.W., et al.Inflammation increases the distribution of dorsal horn neurons that internalize the neurokinin-1 receptor in response to noxious and non-noxious stimulationJ. Neurosci.17(20)8049-8060(1997)