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Transient receptor potential TRPA1 channel desensitization in sensory neurons is agonist dependent and regulated by TRPV1-directed internalization.
J Physiol. 2007 Aug 15; 583(Pt 1):175-93.JP

Abstract

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.

Authors+Show Affiliations

Department of Endodontics, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA. akopian@uthscsa.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17584831

Citation

Akopian, Armen N., et al. "Transient Receptor Potential TRPA1 Channel Desensitization in Sensory Neurons Is Agonist Dependent and Regulated By TRPV1-directed Internalization." The Journal of Physiology, vol. 583, no. Pt 1, 2007, pp. 175-93.
Akopian AN, Ruparel NB, Jeske NA, et al. Transient receptor potential TRPA1 channel desensitization in sensory neurons is agonist dependent and regulated by TRPV1-directed internalization. J Physiol. 2007;583(Pt 1):175-93.
Akopian, A. N., Ruparel, N. B., Jeske, N. A., & Hargreaves, K. M. (2007). Transient receptor potential TRPA1 channel desensitization in sensory neurons is agonist dependent and regulated by TRPV1-directed internalization. The Journal of Physiology, 583(Pt 1), 175-93.
Akopian AN, et al. Transient Receptor Potential TRPA1 Channel Desensitization in Sensory Neurons Is Agonist Dependent and Regulated By TRPV1-directed Internalization. J Physiol. 2007 Aug 15;583(Pt 1):175-93. PubMed PMID: 17584831.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transient receptor potential TRPA1 channel desensitization in sensory neurons is agonist dependent and regulated by TRPV1-directed internalization. AU - Akopian,Armen N, AU - Ruparel,Nikita B, AU - Jeske,Nathaniel A, AU - Hargreaves,Kenneth M, Y1 - 2007/06/21/ PY - 2007/6/23/pubmed PY - 2007/10/31/medline PY - 2007/6/23/entrez SP - 175 EP - 93 JF - The Journal of physiology JO - J Physiol VL - 583 IS - Pt 1 N2 - 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. SN - 0022-3751 UR - https://www.unboundmedicine.com/medline/citation/17584831/Transient_receptor_potential_TRPA1_channel_desensitization_in_sensory_neurons_is_agonist_dependent_and_regulated_by_TRPV1_directed_internalization_ L2 - https://doi.org/10.1113/jphysiol.2007.133231 DB - PRIME DP - Unbound Medicine ER -