Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
Animals
Behavior, Animal
Cell-Free System
Dermatitis, Contact
/ drug therapy
Disease Models, Animal
Ganglia, Spinal
/ metabolism
Humans
Mice, Inbred C57BL
Mice, Knockout
Neurons
/ drug effects
Pruritus
/ drug therapy
Receptors, Atrial Natriuretic Factor
/ agonists
Reproducibility of Results
Signal Transduction
/ drug effects
Small Molecule Libraries
/ chemistry
Journal
Science translational medicine
ISSN: 1946-6242
Titre abrégé: Sci Transl Med
Pays: United States
ID NLM: 101505086
Informations de publication
Date de publication:
10 07 2019
10 07 2019
Historique:
received:
26
09
2018
revised:
19
02
2019
accepted:
30
05
2019
entrez:
12
7
2019
pubmed:
12
7
2019
medline:
25
7
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31292265
pii: 11/500/eaav5464
doi: 10.1126/scitranslmed.aav5464
pmc: PMC7218920
mid: NIHMS1584824
pii:
doi:
Substances chimiques
Small Molecule Libraries
0
Receptors, Atrial Natriuretic Factor
EC 4.6.1.2
atrial natriuretic factor receptor A
EC 4.6.1.2
atrial natriuretic factor receptor B
EC 4.6.1.2
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Intramural NIH HHS
ID : ZIA DE000721
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA TR000053
Pays : United States
Organisme : NIDCR NIH HHS
ID : ZIA DE000721
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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