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Papers of the Week

Papers: 13 Jul 2019 - 19 Jul 2019

Animal Studies


2019 Jul 10

Sci Transl Med



Editor's Pick

Inhibition of natriuretic peptide receptor 1 reduces itch in mice.


Solinski H J, Dranchak P, Oliphant E, Gu X, Earnest TW, Braisted J, Inglese J, Hoon MA
Sci Transl Med. 2019 Jul 10; 11(500).
PMID: 31292265.


There is a major clinical need for new therapies for the treatment of chronic itch. Many of the molecular components involved in itch neurotransmission are known, including the neuropeptide NPPB, a transmitter required for normal itch responses to multiple pruritogens in mice. Here, we investigated the potential for a novel strategy for the treatment of itch that involves the inhibition of the NPPB receptor NPR1 (natriuretic peptide receptor 1). Because there are no available effective human NPR1 (hNPR1) antagonists, we performed a high-throughput cell-based screen and identified 15 small-molecule hNPR1 inhibitors. Using in vitro assays, we demonstrated that these compounds specifically inhibit hNPR1 and murine NPR1 (mNPR1). In vivo, NPR1 antagonism attenuated behavioral responses to both acute itch- and chronic itch-challenged mice. Together, our results suggest that inhibiting NPR1 might be an effective strategy for treating acute and chronic itch.