Research ArticleITCH

Inhibition of natriuretic peptide receptor 1 reduces itch in mice

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Science Translational Medicine  10 Jul 2019:
Vol. 11, Issue 500, eaav5464
DOI: 10.1126/scitranslmed.aav5464

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Let him that itches block NPR1

Chronic itch is an uncomfortable sensation with major impact on the quality of life. The pathophysiology of itch is not clearly elucidated, and the few available treatments are mostly ineffective. The natriuretic peptide receptor 1 (NPR1) has been recently shown to promote itch in mice; however, a peptide NPR1 inhibitor showed poor effects in mice. Investigating the reason for these negative results, Solinski et al. now show that the reported NPR1 inhibitor acted as partial agonist of the receptor, thus explaining the failure in relieving itch. Using high-throughput screening, the authors identified small-molecule human NPR1 antagonists. The molecules were able to relieve chronic itch in mice without inducing adverse effects.