Tacr1, also known as the neurokinin 1 receptor (NK1 receptor), is a G-protein-coupled receptor. It binds to substance P, a neuropeptide, and is involved in multiple physiological and pathophysiological processes. It participates in neural circuits related to pain, touch, sexual behavior, and reward, and may also be involved in tumor-innervation-related metastasis and other pathways. Understanding its function is crucial for comprehending normal biological functions and disease mechanisms, and genetic models like KO/CKO mouse models can greatly assist in its study [1,2,3,4].

In male sexual behavior, chemosensory input activates BNSTprTac1 neurons, which release substance P to potentiate POATacr1 neurons through Tacr1, initiating mating [1]. In breast cancer, neuronal substance P acting on tumoral Tacr1 drives metastasis [2]. In pain-related studies, activation of spinal Tacr1-expressing neurons evokes pain-related behaviors, and neurons in the superior lateral parabrachial nucleus expressing Tacr1 play a role in ongoing pain sensation [4]. Also, in the rostral ventromedial medulla, Tacr1-expressing ON cells inhibit itch [5].

In conclusion, Tacr1 is essential in neural circuits governing male sexual behavior, pain, and itch, and also in breast cancer metastasis. The use of KO/CKO mouse models in these studies has revealed its role in these biological processes and disease conditions, providing insights into potential therapeutic targets for related diseases.

References:

1. Bayless, Daniel W, Davis, Chung-Ha O, Yang, Renzhi, Luo, Liqun, Shah, Nirao M. 2023. A neural circuit for male sexual behavior and reward. In Cell, 186, 3862-3881.e28. doi:10.1016/j.cell.2023.07.021. https://pubmed.ncbi.nlm.nih.gov/37572660/

2. Padmanaban, Veena, Keller, Isabel, Seltzer, Ethan S, Kerner, Zachary, Tavazoie, Sohail F. 2024. Neuronal substance P drives metastasis through an extracellular RNA-TLR7 axis. In Nature, 633, 207-215. doi:10.1038/s41586-024-07767-5. https://pubmed.ncbi.nlm.nih.gov/39112700/

3. Choi, Seungwon, Hachisuka, Junichi, Brett, Matthew A, Ross, Sarah E, Ginty, David D. 2020. Parallel ascending spinal pathways for affective touch and pain. In Nature, 587, 258-263. doi:10.1038/s41586-020-2860-1. https://pubmed.ncbi.nlm.nih.gov/33116307/

4. Barik, Arnab, Sathyamurthy, Anupama, Thompson, James, Levine, Ariel, Chesler, Alexander. 2021. A spinoparabrachial circuit defined by Tacr1 expression drives pain. In eLife, 10, . doi:10.7554/eLife.61135. https://pubmed.ncbi.nlm.nih.gov/33591273/

5. Follansbee, Taylor, Domocos, Dan, Nguyen, Eileen, Ross, Sarah E, Carstens, Earl. 2022. Inhibition of itch by neurokinin 1 receptor (Tacr1) -expressing ON cells in the rostral ventromedial medulla in mice. In eLife, 11, . doi:10.7554/eLife.69626. https://pubmed.ncbi.nlm.nih.gov/35972457/