Neuromedin U receptor 2-deficient mice display differential responses in sensory perception, stress, and feeding.
Neuromedin U (NMU) is a highly conserved neuropeptide with a variety of physiological functions mediated by two receptors, peripheral NMUR1 and central nervous system NMUR2. Here we report the generation and phenotypic characterization of mice deficient in the central nervous system receptor NMUR2. We show that behavioral effects, such as suppression of food intake, enhanced pain response, and excessive grooming induced by intracerebroventricular NMU administration were abolished in the NMUR2 knockout (KO) mice, establishing a causal role for NMUR2 in mediating NMU's central effects on these behaviors. In contrast to the NMU peptide-deficient mice, NMUR2 KO mice appeared normal with regard to stress, anxiety, body weight regulation, and food consumption. However, the NMUR2 KO mice showed reduced pain sensitivity in both the hot plate and formalin tests. Furthermore, facilitated excitatory synaptic transmission in spinal dorsal horn neurons, a mechanism by which NMU stimulates pain, did not occur in NMUR2 KO mice. These results provide significant insights into a functional dissection of the differential contribution of peripherally or centrally acting NMU system. They suggest that NMUR2 plays a more significant role in central pain processing than other brain functions including stress/anxiety and regulation of feeding.
Zeng
Hongkui
H
Nura, Inc., Seattle, WA 98104, USA. hzeng@omeros.com
Gragerov
Alexander
A
Hohmann
John G
JG
Pavlova
Maria N
MN
Schimpf
Brian A
BA
Xu
Hui
H
Wu
Long-Jun
LJ
Toyoda
Hiroki
H
Zhao
Ming-Gao
MG
Rohde
Alex D
AD
Gragerova
Galina
G
Onrust
Rene
R
Bergmann
John E
JE
Zhuo
Min
M
Gaitanaris
George A
GA
D000818:Animals; D001007:Anxiety / Q000235:genetics; D005247:Feeding Behavior / Q000502:physiology*; D005260:Female; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010146:Pain / Q000235:genetics* / Q000503:physiopathology; D010465:Perception / Q000502:physiology*; D017981:Receptors, Neurotransmitter / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D013312:Stress, Physiological / Q000235:genetics*
D008565:Membrane Proteins; D017981:Receptors, Neurotransmitter; C082444:neuromedin U receptor