Neurokinin 2 receptor and Neurokinin 3 receptor (NK2R, NK3R)

Neurokinin 2 receptor and neurokinin 3 receptor are members of the tachykinin receptor family of G protein-coupled receptors, encoded by TACR2 and TACR3 respectively. Both receptors are expressed in the nervous system, smooth muscle, and various peripheral tissues. They are activated by endogenous neuropeptides of the tachykinin family: Neurokinin A preferentially activates NK2R, while Neurokinin B is the primary ligand for NK3R; both can also be activated (less potently) by other tachykinins such as substance P. These receptors mediate diverse physiological effects, including modulation of neurotransmission, smooth muscle contractility, immune regulation, and neuroendocrine signaling. NK2R is especially important in regulating gastrointestinal motility and appetite, while NK3R is crucial in the hypothalamic-pituitary-gonadal axis, behavior, and certain cardiovascular and metabolic functions. Both serve as validated therapeutic targets for a variety of diseases, with drugs in clinical development for disorders such as menopausal symptoms (NK3R antagonists), functional gastrointestinal diseases (NK2R), and possibly cancer and metabolic diseases.

Other names

Neurokinin 2 receptorNK2RTACR2Neurokinin 3 receptorNK3RTACR3Tachykinin receptor 2Tachykinin receptor 3NK-2 receptorNK-3 receptor

Agonists activate receptor, leading to Gq protein coupling, stimulation of phospholipase C, increase in intracellular calcium, and downstream cellular effects. Antagonists block endogenous tachykinin peptides from activating the receptor, inhibiting downstream signaling and related physiological responses.