Substance P (SP), Neurokinin A (NKA) and Neurokinin B (NKB) are all peptides belonging to the Tachykinin protein family. These three peptides, which demonstrate quite a heterogeneity in their distribution, exert their effect via three receptors: Neurokinin 1-3 receptors, members of the G-protein coupled receptor superfamily. However, Neurokinin 1 (NK₁) receptor preferentially binds Substance P, Neurokinin 2 (NK₂) receptor to NKA, and Neurokinin 3 (NK₃) receptor to NKB¹.

Neurokinin receptors are distinguished by their seven transmembrane domains, an extracellular N-terminus and a cytosolic C-terminal. An unusual property of these receptors is the presence of introns as part of their structural organization^1-3. Tachykinin receptors undergo alternative splicing. For example, NK₁ receptor is detected with different C-terminal lengths. The longer receptor isoform is found in the brain whereas the truncated form is mostly detected in the periphery^1,4.

Due to the broad expression profile of tachykinin peptides, their respective receptors are also expressed in a similar fashion. NK₁ receptor is widely expressed in neurons, endothelial cells, muscle and immune system cells. NK₂ receptor is broadly expressed in the periphery and its expression in the brain is quite restricted. NK₃ receptor on the other hand is largely expressed in the central nervous system and is also detected in the uterus, skeletal muscle, lung and liver¹.

Neurokinin receptors have been found in many pathophysiological indications and have therefore become targets for the development of pharmacological compounds. Such indications include cancer, psychological disorders, migraine and various inflammations, just to name a few^5-8.