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Nitro-oleic acid inhibits firing and activates TRPV1- and TRPA1-mediated inward currents in dorsal root ganglion neurons from adult male rats.
J Pharmacol Exp Ther. 2010 Jun; 333(3):883-95.JP

Abstract

Nitro-oleic acid (OA-NO(2)), an electrophilic fatty acid by-product of nitric oxide and nitrite reactions, is present in normal and inflamed mammalian tissues at up to micromolar concentrations and exhibits anti-inflammatory signaling actions. The effects of OA-NO(2) on cultured dorsal root ganglion (DRG) neurons were examined using fura-2 Ca(2+) imaging and patch clamping. OA-NO(2) (3.5-35 microM) elicited Ca(2+) transients in 20 to 40% of DRG neurons, the majority (60-80%) of which also responded to allyl isothiocyanate (AITC; 1-50 microM), a TRPA1 agonist, and to capsaicin (CAPS; 0.5 microM), a TRPV1 agonist. The OA-NO(2)-evoked Ca(2+) transients were reduced by the TRPA1 antagonist 2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl) acetamide (HC-030031; 5-50 microM) and the TRPV1 antagonist capsazepine (10 microM). Patch-clamp recording revealed that OA-NO(2) depolarized and induced inward currents in 62% of neurons. The effects of OA-NO(2) were elicited by concentrations >or=5 nM and were blocked by 10 mM dithiothreitol. Concentrations of OA-NO(2) >or=5 nM reduced action potential (AP) overshoot, increased AP duration, inhibited firing induced by depolarizing current pulses, and inhibited Na(+) currents. The effects of OA-NO(2) were not prevented or reversed by the NO-scavenger carboxy-2-phenyl-4,4,5,5-tetramethylimidazolineoxyl-1-oxyl-3-oxide. A large percentage (46-57%) of OA-NO(2)-responsive neurons also responded to CAPS (0.5 microM) or AITC (0.5 microM). OA-NO(2) currents were reduced by TRPV1 (diarylpiperazine; 5 microM) or TRPA1 (HC-030031; 5 microM) antagonists. These data reveal that endogenous OA-NO(2) generated at sites of inflammation may initially activate transient receptor potential channels on nociceptive afferent nerves, contributing to the initiation of afferent nerve activity, and later suppresses afferent firing.

Authors+Show Affiliations

Department of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania 15261, USA. ads5@pitt.eduNo 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, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20304940

Citation

Sculptoreanu, A, et al. "Nitro-oleic Acid Inhibits Firing and Activates TRPV1- and TRPA1-mediated Inward Currents in Dorsal Root Ganglion Neurons From Adult Male Rats." The Journal of Pharmacology and Experimental Therapeutics, vol. 333, no. 3, 2010, pp. 883-95.
Sculptoreanu A, Kullmann FA, Artim DE, et al. Nitro-oleic acid inhibits firing and activates TRPV1- and TRPA1-mediated inward currents in dorsal root ganglion neurons from adult male rats. J Pharmacol Exp Ther. 2010;333(3):883-95.
Sculptoreanu, A., Kullmann, F. A., Artim, D. E., Bazley, F. A., Schopfer, F., Woodcock, S., Freeman, B. A., & de Groat, W. C. (2010). Nitro-oleic acid inhibits firing and activates TRPV1- and TRPA1-mediated inward currents in dorsal root ganglion neurons from adult male rats. The Journal of Pharmacology and Experimental Therapeutics, 333(3), 883-95. https://doi.org/10.1124/jpet.109.163154
Sculptoreanu A, et al. Nitro-oleic Acid Inhibits Firing and Activates TRPV1- and TRPA1-mediated Inward Currents in Dorsal Root Ganglion Neurons From Adult Male Rats. J Pharmacol Exp Ther. 2010;333(3):883-95. PubMed PMID: 20304940.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nitro-oleic acid inhibits firing and activates TRPV1- and TRPA1-mediated inward currents in dorsal root ganglion neurons from adult male rats. AU - Sculptoreanu,A, AU - Kullmann,F A, AU - Artim,D E, AU - Bazley,F A, AU - Schopfer,F, AU - Woodcock,S, AU - Freeman,B A, AU - de Groat,W C, Y1 - 2010/03/19/ PY - 2010/3/23/entrez PY - 2010/3/23/pubmed PY - 2010/6/12/medline SP - 883 EP - 95 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 333 IS - 3 N2 - Nitro-oleic acid (OA-NO(2)), an electrophilic fatty acid by-product of nitric oxide and nitrite reactions, is present in normal and inflamed mammalian tissues at up to micromolar concentrations and exhibits anti-inflammatory signaling actions. The effects of OA-NO(2) on cultured dorsal root ganglion (DRG) neurons were examined using fura-2 Ca(2+) imaging and patch clamping. OA-NO(2) (3.5-35 microM) elicited Ca(2+) transients in 20 to 40% of DRG neurons, the majority (60-80%) of which also responded to allyl isothiocyanate (AITC; 1-50 microM), a TRPA1 agonist, and to capsaicin (CAPS; 0.5 microM), a TRPV1 agonist. The OA-NO(2)-evoked Ca(2+) transients were reduced by the TRPA1 antagonist 2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl) acetamide (HC-030031; 5-50 microM) and the TRPV1 antagonist capsazepine (10 microM). Patch-clamp recording revealed that OA-NO(2) depolarized and induced inward currents in 62% of neurons. The effects of OA-NO(2) were elicited by concentrations >or=5 nM and were blocked by 10 mM dithiothreitol. Concentrations of OA-NO(2) >or=5 nM reduced action potential (AP) overshoot, increased AP duration, inhibited firing induced by depolarizing current pulses, and inhibited Na(+) currents. The effects of OA-NO(2) were not prevented or reversed by the NO-scavenger carboxy-2-phenyl-4,4,5,5-tetramethylimidazolineoxyl-1-oxyl-3-oxide. A large percentage (46-57%) of OA-NO(2)-responsive neurons also responded to CAPS (0.5 microM) or AITC (0.5 microM). OA-NO(2) currents were reduced by TRPV1 (diarylpiperazine; 5 microM) or TRPA1 (HC-030031; 5 microM) antagonists. These data reveal that endogenous OA-NO(2) generated at sites of inflammation may initially activate transient receptor potential channels on nociceptive afferent nerves, contributing to the initiation of afferent nerve activity, and later suppresses afferent firing. SN - 1521-0103 UR - https://www.unboundmedicine.com/medline/citation/20304940/Nitro_oleic_acid_inhibits_firing_and_activates_TRPV1__and_TRPA1_mediated_inward_currents_in_dorsal_root_ganglion_neurons_from_adult_male_rats_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=20304940 DB - PRIME DP - Unbound Medicine ER -