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

eLife

Jin-Hua Jin¹  Kai-Feng Shen¹  Yu Sun¹  Qing-Tao Meng¹  Ray Kim¹  Li Wan²  Juan Liu³  Hua Jin³  Qianyi Yang³  Jun Yin³  Admire Munanairi³  Devin M Barry³  Fang Gao³  Benlong Liu³  Jiahang Peng³  Xian-Yu Liu³  Zhou-Feng Chen⁴  Xue-Ting Liu⁵  Ailin Tao⁶ 

[1] Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St Louis, United States;Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St Louis, United States;Department of Pain, Guangzhou Medical University, Guangzhou, China;Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St Louis, United States;Departments of Anesthesiology, Washington University School of Medicine, St Louis, United States;Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St Louis, United States;Departments of Anesthesiology, Washington University School of Medicine, St Louis, United States;Developmental Biology, Washington University School of Medicine, St. Louis, United States;The Second Affiliated Hospital, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Guangzhou Medical University, Guangzhou, China;Departments of Medicine, Washington University School of Medicine, St. Louis, United States;Departments of Psychiatry, Washington University School of Medicine, St. Louis, United States;Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St Louis, United States;Developmental Biology, Washington University School of Medicine, St. Louis, United States;The Second Affiliated Hospital, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Guangzhou Medical University, Guangzhou, China;The Second Affiliated Hospital, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Guangzhou Medical University, Guangzhou, China;

关键词: itch;    BNP;    NPRC;    NPRA;    GRP;    spinal cord;    Mouse;   

DOI  :  10.7554/eLife.71689

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY