BNP facilitates NMB-encoded histaminergic itch via NPRC-NMBR crosstalk
- Washington University in St. Louis, United States
- Second Affiliated Hospital of Guangzhou Medical University, China
Abstract
Histamine-dependent and -independent itch is conveyed by parallel peripheral neural pathways that express gastrin-releasing peptide (GRP) and neuromedin B (NMB), respectively, to the spinal cord of mice. B-type natriuretic peptide (BNP) has been proposed to transmit both types of itch via its receptor NPRA encoded by Npr1. However, BNP also binds to its cognate receptor, NPRC encoded by Npr3 with equal potency. Moreover, natriuretic peptides (NP) signal through the Gi-couped inhibitory cGMP pathway that is supposed to inhibit neuronal activity, raising the question of how BNP may transmit itch information. Here we report that Npr3 expression in laminae I-II of the dorsal horn partially overlaps with NMB receptor (NMBR) that transmits histaminergic itch via Gq-couped PLCb-Ca2+ signaling pathway. Functional studies indicate that NPRC is required for itch evoked by histamine but not chloroquine (CQ), a nonhistaminergic pruritogen. Importantly, BNP significantly facilitates scratching behaviors mediated by NMB, but not GRP. Consistently, BNP evoked Ca2+ responses in NMBR/NPRC HEK 293 cells and NMBR/NPRC dorsal horn neurons. These results reveal a previously unknown mechanism by which BNP facilitates NMB-encoded itch through a novel NPRC-NMBR cross-signaling in mice. Our studies uncover distinct modes of action for neuropeptides in transmission and modulation of itch in mice.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figure 1B, C, Figure 1-figure supplement 1A, B, Figure 1-figure supplement 2G, H, Figure 2A-F, Figure 3A-I, Figure 4F, G, Figure 5F, H, I, Figure 6A-C, and Figure 6-figure supplement 1A, B, E.
Article and author information
Author details
Funding
National Institutes of Health (R01NS094344,R01 DA037261-01A1 and R01NS113938-01A1)
- Qing-Tao Meng
- Xian-Yu Liu
- Juan Liu
- Admire Munanairi
- Devin M Barry
- Benlong Liu
- Hua Jin
- Yu Sun
- Qianyi Yang
- Fang Gao
- Li Wan
- Jiahang Peng
- Jin-Hua Jin
- Kai-Feng Shen
- Ray Kim
- Jun Yin
- Zhou-Feng Chen
National Natural Science Foundation of China (82171764)
- Xue-Ting Liu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experiments were performed in accordance with the guidelines of the National Institutes of Health and the International Association for the Study of Pain and were approved by the Animal Studies Committee at Washington University School of Medicine. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols of Washington University School of Medicine (#20190163).
Copyright
© 2021, Meng et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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BNP facilitates NMB-encoded histaminergic itch via NPRC-NMBR crosstalk
eLife 10:e71689.
https://doi.org/10.7554/eLife.71689
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