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Agonist-dependent potentiation of vanilloid receptor transient receptor potential vanilloid type 1 function by stilbene derivatives.
Mol Pharmacol. 2012 May; 81(5):689-700.MP

Abstract

Transient receptor potential vanilloid type 1 (TRPV1) is a nonselective cation channel activated by capsaicin, low pH, and noxious heat and plays a key role in nociception. Understanding mechanisms for functional modulation of TRPV1 has important implications. One characteristic of TRPV1 is that channel activity induced by either capsaicin or other activators can be sensitized or modulated by factors involving different cell signaling mechanisms. In this study, we describe a novel mechanism for the modulation of TRPV1 function: TRPV1 function is modulated by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) and its analogs. We found that, in rat dorsal root ganglion neurons, although DIDS did not induce the activation of TRPV1 per se but drastically increased the TRPV1 currents induced by either capsaicin or low pH. DIDS also blocked the tachyphylaxis of the low pH-induced TRPV1 currents. 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS), a DIDS analog, failed to enhance the capsaicin-evoked TRPV1 current but increased the low pH-evoked TRPV1 currents, with an effect comparable with that of DIDS. SITS also blocked the low pH-induced tachyphylaxis. DIDS also potentiated the currents of TRPV1 channels expressed in human embryonic kidney 293 cells, with an effect of left-shifting the concentration-response curve of the capsaicin-induced TRPV1 currents. This study demonstrates that DIDS and SITS, traditionally used chloride channel blockers, can modify TRPV1 channel function in an agonist-dependent manner. The results provide new input for understanding TRPV1 modulation and developing new modulators of TRPV1 function.

Authors+Show Affiliations

Department of Pharmacology, Hebei Medical University, Shijiazhuang, Hebei 050017, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22328719

Citation

Zhang, Xuan, et al. "Agonist-dependent Potentiation of Vanilloid Receptor Transient Receptor Potential Vanilloid Type 1 Function By Stilbene Derivatives." Molecular Pharmacology, vol. 81, no. 5, 2012, pp. 689-700.
Zhang X, Du XN, Zhang GH, et al. Agonist-dependent potentiation of vanilloid receptor transient receptor potential vanilloid type 1 function by stilbene derivatives. Mol Pharmacol. 2012;81(5):689-700.
Zhang, X., Du, X. N., Zhang, G. H., Jia, Z. F., Chen, X. J., Huang, D. Y., Liu, B. Y., & Zhang, H. L. (2012). Agonist-dependent potentiation of vanilloid receptor transient receptor potential vanilloid type 1 function by stilbene derivatives. Molecular Pharmacology, 81(5), 689-700. https://doi.org/10.1124/mol.111.076000
Zhang X, et al. Agonist-dependent Potentiation of Vanilloid Receptor Transient Receptor Potential Vanilloid Type 1 Function By Stilbene Derivatives. Mol Pharmacol. 2012;81(5):689-700. PubMed PMID: 22328719.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Agonist-dependent potentiation of vanilloid receptor transient receptor potential vanilloid type 1 function by stilbene derivatives. AU - Zhang,Xuan, AU - Du,Xiao-Na, AU - Zhang,Guo-Hong, AU - Jia,Zhan-Feng, AU - Chen,Xing-Juan, AU - Huang,Dong-Yang, AU - Liu,Bo-Yi, AU - Zhang,Hai-Lin, Y1 - 2012/02/10/ PY - 2012/2/14/entrez PY - 2012/2/14/pubmed PY - 2012/6/8/medline SP - 689 EP - 700 JF - Molecular pharmacology JO - Mol Pharmacol VL - 81 IS - 5 N2 - Transient receptor potential vanilloid type 1 (TRPV1) is a nonselective cation channel activated by capsaicin, low pH, and noxious heat and plays a key role in nociception. Understanding mechanisms for functional modulation of TRPV1 has important implications. One characteristic of TRPV1 is that channel activity induced by either capsaicin or other activators can be sensitized or modulated by factors involving different cell signaling mechanisms. In this study, we describe a novel mechanism for the modulation of TRPV1 function: TRPV1 function is modulated by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) and its analogs. We found that, in rat dorsal root ganglion neurons, although DIDS did not induce the activation of TRPV1 per se but drastically increased the TRPV1 currents induced by either capsaicin or low pH. DIDS also blocked the tachyphylaxis of the low pH-induced TRPV1 currents. 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS), a DIDS analog, failed to enhance the capsaicin-evoked TRPV1 current but increased the low pH-evoked TRPV1 currents, with an effect comparable with that of DIDS. SITS also blocked the low pH-induced tachyphylaxis. DIDS also potentiated the currents of TRPV1 channels expressed in human embryonic kidney 293 cells, with an effect of left-shifting the concentration-response curve of the capsaicin-induced TRPV1 currents. This study demonstrates that DIDS and SITS, traditionally used chloride channel blockers, can modify TRPV1 channel function in an agonist-dependent manner. The results provide new input for understanding TRPV1 modulation and developing new modulators of TRPV1 function. SN - 1521-0111 UR - https://www.unboundmedicine.com/medline/citation/22328719/Agonist_dependent_potentiation_of_vanilloid_receptor_transient_receptor_potential_vanilloid_type_1_function_by_stilbene_derivatives_ L2 - http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=22328719 DB - PRIME DP - Unbound Medicine ER -