Neuromedin U receptor 1 (NMUR1) and Neuromedin U receptor 2 (NMUR2) (NMUR1/NMUR2)

Neuromedin U receptors (NMUR1 and NMUR2) are G protein-coupled receptors that serve as the primary mediators for the neuropeptides Neuromedin U (NMU) and Neuromedin S (NMS) [1, 10]. NMUR1 is predominantly expressed in peripheral tissues, including the gastrointestinal tract, lungs, and various immune cells such as group 2 innate lymphoid cells (ILC2s), where it plays a significant role in regulating smooth muscle contraction and promoting type 2 inflammatory responses [4, 5, 7]. In contrast, NMUR2 is primarily localized within the central nervous system, particularly in the hypothalamus and spinal cord, where it is involved in the regulation of energy homeostasis, feeding behavior, circadian rhythms, and nociception [1, 3, 6]. Due to their potent anorexigenic effects, these receptors—especially NMUR2—are major targets for the development of anti-obesity therapeutics, while NMUR1 is investigated for its roles in asthma and cancer immunotherapy [8, 12, 14]. Pharmacological modulation of these receptors involves agonists for metabolic control and antagonists for inflammatory or pain-related conditions, though therapeutic development must address challenges such as cardiovascular side effects and the complex distribution of the two subtypes [3, 6, 12]. The pleiotropic nature of NMU signaling across different tissues presents a significant challenge in achieving therapeutic selectivity without inducing adverse systemic effects [3, 14].

Other names

Neuromedin U receptorNMURsGPR66FM-3NMU1RTGR-1FM-4NMU2R

Agonists bind to NMUR1 or NMUR2, activating Gq/11 or Gi protein signaling pathways, which leads to intracellular calcium mobilization, inhibition of cAMP production, and activation of the ERK/MAPK pathway to regulate metabolism, inflammation, and muscle tone [1, 5, 6, 11].