BNP facilitates NMB-encoded histaminergic itch via NPRC-NMBR crosstalk

Author:

Meng Qing-Tao1,Liu Xian-Yu12,Liu Xue-Ting134ORCID,Liu Juan12ORCID,Munanairi Admire12,Barry Devin M12,Liu Benlong12,Jin Hua12,Sun Yu1,Yang Qianyi12,Gao Fang12,Wan Li15,Peng Jiahang12,Jin Jin-Hua1,Shen Kai-Feng1,Kim Ray1,Yin Jun12,Tao Ailin4,Chen Zhou-Feng12346ORCID

Affiliation:

1. Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine

2. Departments of Anesthesiology, Washington University School of Medicine

3. Developmental Biology, Washington University School of Medicine

4. The Second Affiliated Hospital, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Guangzhou Medical University

5. Department of Pain, Guangzhou Medical University

6. Departments of Medicine, Washington University School of Medicine

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 PLCβ-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.

Funder

National Institutes of Health

National Natural Science Foundation of China

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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