Conopeptides promote itch through human itch receptor hMgprX1

Toxicon : Official Journal of the International Society on Toxinology
Samuel S EspinoQin Liu

Abstract

Members of Mas related G-protein coupled receptors (Mrgpr) are known to mediate itch. To date, several compounds have been shown to activate these receptors, including chloroquine, a common antimalarial drug, and peptides of the RF-amide family. However, specific ligands for these receptors are still lacking and there is a need for novel compounds that can be used to modulate the receptors in order to understand the cellular and molecular mechanism in which they mediate itch. Some cone snail venoms were previously shown to induce itch in mice. Here, we show that the venom of Conus textile induces itch through activation of itch-sensing sensory neurons, marked by their sensitivity to chloroquine. Two RF-amide peptides, CNF-Tx1 and CNF-Tx2, were identified in a C. textile venom gland transcriptome. These belong to the conorfamide family of peptides which includes previously described peptides from the venoms of Conus victoriae (CNF-Vc1) and Conus spurius (CNF-Sr1 and CNF-Sr2). We show that CNF-Vc1 and CNF-Sr1 activate MrgprC11 whereas CNF-Vc1 and CNF-Tx2 activate the human MrgprX1 (hMrgprX1). The peptides CNF-Tx1 and CNF-Sr2 do not activate MrgprC11 or hMrgprX1. Intradermal injection of CNF-Vc1 and CNF-Tx2 into the cheek of a tra...Continue Reading

Citations

Feb 7, 2020·Natural Product Reports·Anthony R CarrollMichèle R Prinsep
Mar 26, 2021·Journal of Natural Products·Gabriel D BosseJoanna Gajewiak
Feb 23, 2021·The Journal of Allergy and Clinical Immunology·Katharina WolfAndreas E Kremer
Jun 8, 2021·RSC Medicinal Chemistry·Ashlin TurnerDavid J Craik
Sep 1, 2021·British Journal of Pharmacology·Laurent MiseryCyril Leven

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