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Nitro-oleic acid desensitizes TRPA1 and TRPV1 agonist responses in adult rat DRG neurons.
Exp Neurol. 2014 Jan; 251:12-21.EN

Abstract

Nitro-oleic acid (OA-NO2), an electrophilic fatty acid nitroalkene byproduct of redox reactions, activates transient receptor potential ion channels (TRPA1 and TRPV1) in primary sensory neurons. To test the possibility that signaling actions of OA-NO2 might modulate TRP channels, we examined: (1) interactions between OA-NO2 and other agonists for TRPA1 (allyl-isothiocyanate, AITC) and TRPV1 (capsaicin) in rat dissociated dorsal root ganglion cells using Ca(2+) imaging and patch clamp techniques and (2) interactions between these agents on sensory nerves in the rat hindpaw. Ca(2+) imaging revealed that brief application (15-30 s) of each of the three agonists induced homologous desensitization. Heterologous desensitization also occurred when one agonist was applied prior to another agonist. OA-NO2 was more effective in desensitizing the response to AITC than the response to capsaicin. Prolonged exposure to OA-NO2 (20 min) had a similar desensitizing effect on AITC or capsaicin. Homologous and heterologous desensitizations were also demonstrated with patch clamp recording. Deltamethrin, a phosphatase inhibitor, reduced the capsaicin or AITC induced desensitization of OA-NO2 but did not suppress the OA-NO2 induced desensitization of AITC or capsaicin, indicating that heterologous desensitization induced by either capsaicin or AITC occurs by a different mechanism than the desensitization produced by OA-NO2. Subcutaneous injection of OA-NO2 (2.5mM, 35 μl) into a rat hindpaw induced delayed and prolonged nociceptive behavior. Homologous desensitization occurred with AITC and capsaicin when applied at 15 minute intervals, but did not occur with OA-NO2 when applied at a 30 min interval. Pretreatment with OA-NO2 reduced AITC-evoked nociceptive behaviors but did not alter capsaicin responses. These results raise the possibility that OA-NO2 might be useful clinically to reduce neurogenic inflammation and certain types of painful sensations by desensitizing TRPA1 expressing nociceptive afferents.

Authors+Show Affiliations

Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Urology, The Second Hospital of Shandong University, Jinan, Shandong, PR China. Electronic address: xiz50@pitt.edu.Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Pub Type(s)

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

Language

eng

PubMed ID

24212047

Citation

Zhang, Xiulin, et al. "Nitro-oleic Acid Desensitizes TRPA1 and TRPV1 Agonist Responses in Adult Rat DRG Neurons." Experimental Neurology, vol. 251, 2014, pp. 12-21.
Zhang X, Koronowski KB, Li L, et al. Nitro-oleic acid desensitizes TRPA1 and TRPV1 agonist responses in adult rat DRG neurons. Exp Neurol. 2014;251:12-21.
Zhang, X., Koronowski, K. B., Li, L., Freeman, B. A., Woodcock, S., & de Groat, W. C. (2014). Nitro-oleic acid desensitizes TRPA1 and TRPV1 agonist responses in adult rat DRG neurons. Experimental Neurology, 251, 12-21. https://doi.org/10.1016/j.expneurol.2013.10.020
Zhang X, et al. Nitro-oleic Acid Desensitizes TRPA1 and TRPV1 Agonist Responses in Adult Rat DRG Neurons. Exp Neurol. 2014;251:12-21. PubMed PMID: 24212047.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nitro-oleic acid desensitizes TRPA1 and TRPV1 agonist responses in adult rat DRG neurons. AU - Zhang,Xiulin, AU - Koronowski,Kevin B, AU - Li,Lu, AU - Freeman,Bruce A, AU - Woodcock,Stephen, AU - de Groat,William C, Y1 - 2013/11/08/ PY - 2013/07/25/received PY - 2013/10/14/revised PY - 2013/10/31/accepted PY - 2013/11/12/entrez PY - 2013/11/12/pubmed PY - 2014/2/20/medline KW - AITC KW - DRG KW - Desensitization KW - Nitro-oleic acid KW - Nociception KW - OA-NO(2) KW - Primary sensory neuron KW - TRP channels KW - allyl-isothiocyanate KW - dorsal root ganglion KW - nitro-oleic acid SP - 12 EP - 21 JF - Experimental neurology JO - Exp Neurol VL - 251 N2 - Nitro-oleic acid (OA-NO2), an electrophilic fatty acid nitroalkene byproduct of redox reactions, activates transient receptor potential ion channels (TRPA1 and TRPV1) in primary sensory neurons. To test the possibility that signaling actions of OA-NO2 might modulate TRP channels, we examined: (1) interactions between OA-NO2 and other agonists for TRPA1 (allyl-isothiocyanate, AITC) and TRPV1 (capsaicin) in rat dissociated dorsal root ganglion cells using Ca(2+) imaging and patch clamp techniques and (2) interactions between these agents on sensory nerves in the rat hindpaw. Ca(2+) imaging revealed that brief application (15-30 s) of each of the three agonists induced homologous desensitization. Heterologous desensitization also occurred when one agonist was applied prior to another agonist. OA-NO2 was more effective in desensitizing the response to AITC than the response to capsaicin. Prolonged exposure to OA-NO2 (20 min) had a similar desensitizing effect on AITC or capsaicin. Homologous and heterologous desensitizations were also demonstrated with patch clamp recording. Deltamethrin, a phosphatase inhibitor, reduced the capsaicin or AITC induced desensitization of OA-NO2 but did not suppress the OA-NO2 induced desensitization of AITC or capsaicin, indicating that heterologous desensitization induced by either capsaicin or AITC occurs by a different mechanism than the desensitization produced by OA-NO2. Subcutaneous injection of OA-NO2 (2.5mM, 35 μl) into a rat hindpaw induced delayed and prolonged nociceptive behavior. Homologous desensitization occurred with AITC and capsaicin when applied at 15 minute intervals, but did not occur with OA-NO2 when applied at a 30 min interval. Pretreatment with OA-NO2 reduced AITC-evoked nociceptive behaviors but did not alter capsaicin responses. These results raise the possibility that OA-NO2 might be useful clinically to reduce neurogenic inflammation and certain types of painful sensations by desensitizing TRPA1 expressing nociceptive afferents. SN - 1090-2430 UR - https://www.unboundmedicine.com/medline/citation/24212047/Nitro_oleic_acid_desensitizes_TRPA1_and_TRPV1_agonist_responses_in_adult_rat_DRG_neurons_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(13)00323-3 DB - PRIME DP - Unbound Medicine ER -