Endothelin-1 activates ETA receptors to cause reflex scratching in BALB/c mice
Article first published online: 29 JAN 2009
2007 British Pharmacological Society
British Journal of Pharmacology
Volume 151, Issue 2, pages 278–284, May 2007
How to Cite
McQueen, D. S., Noble, M. A. H. and Bond, S. M. (2007), Endothelin-1 activates ETA receptors to cause reflex scratching in BALB/c mice. British Journal of Pharmacology, 151: 278–284. doi: 10.1038/sj.bjp.0707216
- Issue published online: 29 JAN 2009
- Article first published online: 29 JAN 2009
- (Received November 27, 2006, Accepted January 31, 2007)
- ETA receptors;
- ETB receptors;
- BALB/c mice;
Background and purpose:
Endothelin-1 (ET-1) is present in murine and human skin and causes itch (pruritus) when injected in humans. This behavioural study examined the scratch reflex evoked by ET-1 in mice.
An automated detector was used to determine whether ET-1 causes reflex scratching, the behavioural correlate of itching, in BALB/c mice. Selective agonists and antagonists were used to probe the ET receptor(s) involved.
ET-1 evoked dose-related reflex scratching lasting up to 20 min following intradermal injection (0.1-100 ng; 0.04-40 pmol). The ED50 for ET-1 induced scratching was 2.1 ng and desensitization occurred with cumulative dosing. High doses of the ETB receptor agonist IRL1620 (10 μg; 5.5 nmol), also caused scratching (ED50 1.3 μg, 0.7 nmol). The ETA receptor antagonist BQ123 significantly reduced scratching evoked by ET-1 and IRL 1620, suggesting that both agonists caused scratching via an ETA receptor-dependent mechanism. The ETB receptor antagonist BQ788 significantly reduced scratching evoked by IRL1620 but had no effect on scratching evoked by ET-1. This indicated that activation of ETB receptors by high doses of ETB agonist, but not ET-1, can trigger scratching.
Conclusion and implications:
ET-1 is a potent endogenous activator of reflex scratching (itch). Mechanisms for ET-induced scratching are considered, including direct action of ET-1 on pruriceptive nerve endings and indirect actions via release of endogenous mediators such as histamine from mast cells. ET-1 and ETA receptors, possibly also ETB receptors, are potential targets for developing specific anti-pruritic drugs to treat pruritic skin disorders such as atopic dermatitis.
British Journal of Pharmacology (2007) 151, 278–284. doi:10.1038/sj.bjp.0707216