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Endothelin-B receptor activation triggers an endogenous analgesic cascade at sites of peripheral injury.

Authors: Khodorova, A  Navarro, B  Jouaville, LS  Murphy, JE  Rice, FL  Mazurkiewicz, JE  Long-Woodward, D  Stoffel, M  Strichartz, GR  Yukhananov, R  Davar, G 
Citation: Khodorova A, etal., Nat Med. 2003 Aug;9(8):1055-61. Epub 2003 Jun 29.
Pubmed: (View Article at PubMed) PMID:12847519
DOI: Full-text: DOI:10.1038/nm885

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 (ET(A)) receptors of local nociceptors, it can coincidentally produce analgesia through endothelin-B (ET(B)) receptors. Here we map a new endogenous analgesic circuit, in which ET(B) receptor activation induces the release of beta-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 ET(B) receptor-operated opioid pool.


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CRRD Object Information
CRRD ID: 1581889
Created: 2006-10-30
Species: All species
Last Modified: 2006-10-30
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.