Tachykinin receptor 3 (NK3R)

Tachykinin receptor 3 (NK3R) is a G protein-coupled receptor encoded by the TACR3 gene, primarily expressed in the central nervous system, especially the hypothalamus, hippocampus, and substantia nigra. It acts as the main receptor for the endogenous neuropeptide neurokinin B (NKB) and is involved in diverse functions such as neuroendocrine regulation, specifically controlling gonadotropin-releasing hormone secretion and the hypothalamic-pituitary-gonadal axis. NK3R is also implicated in neuronal excitation, appetite regulation, and angiogenesis. Clinically, it is a therapeutic target for treating menopausal vasomotor symptoms and is under investigation for oncological and neuropsychiatric conditions. A variety of agonists and antagonists, notably fezolinetant, elinzanetant, osanetant, and senktide, modulate its activity for research and clinical purposes. NK3R utilizes the Gq/11 signaling pathway, leading to downstream effects such as increased intracellular calcium and gene regulation. Potential safety concerns include hormonal disruption and off-target tachykinin receptor activity, though drugs targeting NK3R are generally well tolerated in recent clinical trials.

Other names

Neurokinin-3 receptorTACR3NK-3 receptorNK3 receptorHH11

Antagonists inhibit NK3R-mediated signaling pathways, affecting gonadotropin-releasing hormone (GnRH) release and treating hot flashes or vasomotor symptoms. Agonists stimulate Gq/11 protein-coupled receptor signaling, leading to increased neuronal excitation, gene regulation, and downstream functional effects (including anti-angiogenesis in oncology contexts).