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This Article Full Text Full Text (PDF) Supplemental data All Versions of this Article: 583/1/175    most recent jphysiol.2007.133231v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Akopian, A. N. Articles by Hargreaves, K. M. Search for Related Content PubMed PubMed Citation Articles by Akopian, A. N. Articles by Hargreaves, K. M. Related Collections Neuroscience

Departments of
¹ Endodontics
² Cellular and Structural Biology
³ Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA

The pharmacological desensitization of receptors is a fundamental mechanism for regulating the activity of neuronal systems. The TRPA1 channel plays a key role in the processing of noxious information and can undergo functional desensitization by unknown mechanisms. Here we show that TRPA1 is desensitized by homologous (mustard oil; a TRPA1 agonist) and heterologous (capsaicin; a TRPV1 agonist) agonists via Ca²⁺-independent and Ca²⁺-dependent pathways, respectively, in sensory neurons. The pharmacological desensitization of TRPA1 by capsaicin and mustard oil is not influenced by activation of protein phosphatase 2B. However, it is regulated by phosphatidylinositol-4,5-bisphosphate depletion after capsaicin, but not mustard oil, application. Using a biosensor, we establish that capsaicin, unlike mustard oil, consistently activates phospholipase C in sensory neurons. We next demonstrate that TRPA1 desensitization is regulated by TRPV1, and it appears that mustard oil-induced TRPA1 internalization is prevented by coexpression with TRPV1 in a heterologous expression system and in sensory neurons. In conclusion, we propose novel mechanisms whereby TRPA1 activity undergoes pharmacological desensitization through multiple cellular pathways that are agonist dependent and modulated by TRPV1.

(Received 22 March 2007; accepted after revision 15 June 2007; first published online 21 June 2007)
Corresponding author: A. N. Akopian, University of Texas Health Science Center @ San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA. Email: akopian{at}uthscsa.edu

This article has been cited by other articles:

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