Comparison of mice deficient in the high- or low-affinity neurotensin receptors, Ntsr1 or Ntsr2, reveals a novel function for Ntsr2 in thermal nociception.
Neurotensin (NT) is a neuropeptide that induces a wide range of biological activities including hypothermia and analgesia. Such effects are mediated by the NT receptors Ntsr1, Ntsr2 and Ntsr3, although the involvement of each receptor in specific NT functions remains unknown. To address nociceptive function in vivo, we generated both Ntsr1-deficient and Ntsr2-deficient mice. In addition, histochemical analyses of both Ntsr1 and Ntsr2 mRNAs were performed in the mouse brain regions involved in NT-related nociception. The expression of Ntsr2 mRNA was greater than that of Ntsr1 in the periaqueductal gray (PAG) and the rostral ventral medulla (RVM). The mutant and control mice were subjected to the examination of thermal nociception, and in the hot plate test, a significant alteration in jump latency was observed in Ntsr2-deficient mice compared to Ntsr1-deficient or wild-type control mice. Latencies of tail flick and hind paw licking of the mutant mice were not affected compared to control mice. These results suggest that Ntsr2 has an important role in thermal nociception compared to Ntsr1, and that these mutant mice may represent a useful tool for the development of analgesic drugs.
Maeno
Hiroshi
H
Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, Tokyo 187-8502, Japan. maeno@ncnp.go.jp
Yamada
Kazuyuki
K
Santo-Yamada
Yuko
Y
Aoki
Kumiko
K
Sun
Ying-Jie
YJ
Sato
Eiichi
E
Fukushima
Tatsuo
T
Ogura
Hiroo
H
Araki
Tsutomu
T
Kamichi
Sari
S
Kimura
Ichiro
I
Yamano
Mariko
M
Maeno-Hikichi
Yuka
Y
Watase
Kei
K
Aoki
Shunsuke
S
Kiyama
Hiroshi
H
Wada
Etsuko
E
Wada
Keiji
K
D000818:Animals; D001522:Behavior, Animal; D003001:Cloning, Molecular / Q000379:methods; D005786:Gene Expression Regulation; D006358:Hot Temperature / Q000009:adverse effects; D017403:In Situ Hybridization / Q000379:methods; D008526:Medulla Oblongata / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009496:Neurotensin / Q000378:metabolism; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology; D010487:Periaqueductal Gray / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011930:Reaction Time; D018028:Receptors, Neurotensin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
C490984:Ntsr2 protein, mouse; D012333:RNA, Messenger; D018028:Receptors, Neurotensin; C114036:neurotensin type 1 receptor; D009496:Neurotensin