TY - JOUR
T1 - Neuromedin U receptor 2-deficient mice display differential responses in sensory perception, stress, and feeding
AU - Zeng, Hongkui
AU - Gragerov, Alexander
AU - Hohmann, John G.
AU - Pavlova, Maria N.
AU - Schimpf, Brian A.
AU - Xu, Hui
AU - Wu, Long Jun
AU - Toyoda, Hiroki
AU - Zhao, Ming Gao
AU - Rohde, Alex D.
AU - Gragerova, Galina
AU - Onrust, Rene
AU - Bergmann, John E.
AU - Zhuo, Min
AU - Gaitanaris, George A.
PY - 2006/12
Y1 - 2006/12
N2 - 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.
AB - 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.
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U2 - 10.1128/MCB.01148-06
DO - 10.1128/MCB.01148-06
M3 - Article
C2 - 17030627
AN - SCOPUS:33845407004
SN - 0270-7306
VL - 26
SP - 9352
EP - 9363
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 24
ER -