TY - JOUR TI - BNP facilitates NMB-encoded histaminergic itch via NPRC-NMBR crosstalk AU - Meng, Qing-Tao AU - Liu, Xian-Yu AU - Liu, Xue-Ting AU - Liu, Juan AU - Munanairi, Admire AU - Barry, Devin M AU - Liu, Benlong AU - Jin, Hua AU - Sun, Yu AU - Yang, Qianyi AU - Gao, Fang AU - Wan, Li AU - Peng, Jiahang AU - Jin, Jin-Hua AU - Shen, Kai-Feng AU - Kim, Ray AU - Yin, Jun AU - Tao, Ailin AU - Chen, Zhou-Feng A2 - Chiu, Isaac M A2 - Aldrich, Richard W VL - 10 PY - 2021 DA - 2021/12/17 SP - e71689 C1 - eLife 2021;10:e71689 DO - 10.7554/eLife.71689 UR - https://doi.org/10.7554/eLife.71689 AB - 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 PLCĪ²-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. KW - itch KW - BNP KW - NPRC KW - NPRA KW - GRP KW - spinal cord JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -