Cross-inhibition of NMBR and GRPR signaling maintains normal histaminergic itch transmission

Zhong Qiu Zhao, Li Wan, Xian Yu Liu, Fu Quan Huo, Hui Li, Devin M. Barry, Seungil Kim, Zhong Chun Liu, Zhou Feng Chen, Zhong Qiu Zhao, Li Wan, Xian Yu Liu, Fu Quan Huo, Hui Li, Devin M. Barry, Seungil Kim, Zhong Chun Liu, Zhou Feng Chen, Zhou Feng Chen, Zhou Feng ChenStephanie Krieger, Buck E. Rogers, Jinbin Xu, Li Wan, Hui Li, Yun Qing Li, Seungil Kim, Zhong Chun Liu, Fu Quan Huo

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

We previously showed that gastrin-releasing peptide receptor (GRPR) in the spinal cord is important for mediating nonhistaminergic itch. Neuromedin B receptor (NMBR), the second member of the mammalian bombesin receptor family, is expressed in a largely nonoverlapping pattern with GRPR in the superficial spinal cord, and its role in itch transmission remains unclear. Here, we report that Nmbr knock-out (KO) mice exhibited normal scratching behavior in response to intradermal injection of pruritogens. However, mice lacking both Nmbr and Grpr (DKO mice) showed significant deficits in histaminergic itch. In contrast, the chloroquine (CQ)-evoked scratching behavior of DKO mice is not further reduced compared with Grpr KO mice. These results suggest that NMBR and GRPR could compensate for the loss of each other to maintain normal histamine-evoked itch, whereas GRPR is exclusively required for CQ-evoked scratching behavior. Interestingly, GRPR activity is enhanced in Nmbr KO mice despite the lack of upregulation of Grpr expression; so is NMBR in Grpr KO mice. We found that NMB acts exclusively through NMBR for itch transmission, whereas GRP can signal through both receptors, albeit to NMBR to a much lesser extent. Although NMBR and NMBR+ neurons are dispensable for histaminergic itch, GRPR+ neurons are likely to act downstream of NMBR+ neurons to integrate NMB-NMBR-encoded histaminergic itch information in normal physiological conditions. Together, we define the respective function of NMBR and GRPR in itch transmission, and reveal an unexpected relationship not only between the two receptors but also between the two populations of interneurons in itch signaling.

Original languageEnglish
Pages (from-to)12402-12414
Number of pages13
JournalJournal of Neuroscience
Volume34
Issue number37
DOIs
StatePublished - Sep 10 2014

Keywords

  • Cross-inhibition
  • GRP
  • GRPR
  • Itch
  • NMB
  • NMBR

Fingerprint Dive into the research topics of 'Cross-inhibition of NMBR and GRPR signaling maintains normal histaminergic itch transmission'. Together they form a unique fingerprint.

  • Cite this

    Zhao, Z. Q., Wan, L., Liu, X. Y., Huo, F. Q., Li, H., Barry, D. M., Kim, S., Liu, Z. C., Chen, Z. F., Zhao, Z. Q., Wan, L., Liu, X. Y., Huo, F. Q., Li, H., Barry, D. M., Kim, S., Liu, Z. C., Chen, Z. F., Chen, Z. F., ... Huo, F. Q. (2014). Cross-inhibition of NMBR and GRPR signaling maintains normal histaminergic itch transmission. Journal of Neuroscience, 34(37), 12402-12414. https://doi.org/10.1523/JNEUROSCI.1709-14.2014