NK1 receptor

NK1 receptor, also known as the substance P receptor, is a G protein-coupled receptor (GPCR) found in the nervous system of humans and many other species. It is encoded by the TACR1 gene in humans. The NK1 receptor is one of the three neurokinin receptors, with the others being NK2 and NK3, which respond to the tachykinin neuropeptides. Substance P, a key neurotransmitter and neuromodulator that plays a significant role in the regulation of pain, is the most potent ligand for the NK1 receptor.

Function

The NK1 receptor is involved in various biological processes, including pain perception, stress, anxiety, nausea, and vomiting. Activation of the NK1 receptor by substance P in the central and peripheral nervous system can lead to the transmission of pain signals and the initiation of inflammatory responses. In the brain, NK1 receptors are thought to be involved in the regulation of mood and anxiety, as well as the stress response.

Clinical Significance

Due to its role in pain and emotion regulation, the NK1 receptor has been a target for drug development, particularly for analgesics and antiemetics. Aprepitant and Fosaprepitant are examples of NK1 receptor antagonists that have been approved for the prevention of chemotherapy-induced nausea and vomiting (CINV). Research is ongoing into NK1 receptor antagonists as potential treatments for depression, anxiety, and other conditions.

Pharmacology

NK1 receptor antagonists work by blocking the action of substance P at the NK1 receptor, thereby inhibiting the transmission of pain and the inflammatory response. These antagonists have shown efficacy in various models of pain and inflammation, as well as in clinical trials for CINV. The development of NK1 receptor antagonists has been challenging, with many compounds showing efficacy in preclinical models but failing in clinical trials for pain management.

Genetics

The human gene encoding the NK1 receptor, TACR1, is located on chromosome 2. Variations in this gene have been studied in the context of their potential association with psychiatric disorders, pain sensitivity, and response to treatment with NK1 receptor antagonists.

See Also

• Neurokinin A
• Neurokinin B
• G protein-coupled receptor
• Pain management
• Chemotherapy-induced nausea and vomiting