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B-type natriuretic peptide (BNP) has been proposed to transmit both types of itch via its receptor NPRA encoded by\n                    <jats:italic>Npr1<\/jats:italic>\n                    . However, BNP also binds to its cognate receptor, NPRC encoded by\n                    <jats:italic>Npr3<\/jats:italic>\n                    with equal potency. Moreover, natriuretic peptides (NP) signal through the G\n                    <jats:sub>i<\/jats:sub>\n                    -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\n                    <jats:italic>Npr3<\/jats:italic>\n                    expression in laminae I-II of the dorsal horn partially overlaps with NMB receptor (NMBR) that transmits histaminergic itch via G\n                    <jats:sub>q<\/jats:sub>\n                    -couped PLC\u03b2-Ca\n                    <jats:sup>2+<\/jats:sup>\n                    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 Ca\n                    <jats:sup>2+<\/jats:sup>\n                    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.\n                  <\/jats:p>","DOI":"10.7554\/elife.71689","type":"journal-article","created":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T07:15:20Z","timestamp":1639725320000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.71689","source":"Crossref","is-referenced-by-count":20,"title":["BNP facilitates NMB-encoded histaminergic itch via NPRC-NMBR crosstalk"],"prefix":"10.7554","volume":"10","author":[{"given":"Qing-Tao","family":"Meng","sequence":"first","affiliation":[{"name":"Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine","place":["St Louis, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian-Yu","family":"Liu","sequence":"first","affiliation":[{"name":"Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine","place":["St Louis, United 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