Endothelin-B receptor activation triggers an endogenous analgesic cascade at sites of peripheral inj
Author: ["Alla Khodorova","Betsy Navarro","Laurence Sophie Jouaville","Jo-Ellen Murphy","Frank L Rice","Joseph E Mazurkiewicz","Denise Long-Woodward","Markus Stoffel","Gary R Strichartz","Rus Yukhananov","Gudarz Davar"]
Publication: Nature Medicine
CITE.CC academic search helps you expand the influence of your papers.
Abstract
Endothelin-1 (ET-1) is a newly described pain mediator that is involved in the pathogenesis of pain states ranging from trauma to cancer. ET-1 is synthesized by keratinocytes in normal skin and is locally released after cutaneous injury. While it is able to trigger pain through its actions on endothelin-A (ETA) receptors of local nociceptors, it can coincidentally produce analgesia through endothelin-B (ETB) receptors. Here we map a new endogenous analgesic circuit, in which ETB receptor activation induces the release of β-endorphin from keratinocytes and the activation of G-protein-coupled inwardly rectifying potassium channels (GIRKs, also named Kir-3) linked to opioid receptors on nociceptors. These results indicate the existence of an intrinsic feedback mechanism to control peripheral pain in skin, and establish keratinocytes as an ETB receptor–operated opioid pool.
Cite this article
Khodorova, A., Navarro, B., Jouaville, L. et al. Endothelin-B receptor activation triggers an endogenous analgesic cascade at sites of peripheral injury. Nat Med 9, 1055–1061 (2003). https://doi.org/10.1038/nm885
