| Nitro-oleic acid targets transient receptor potential (TRP) channels in capsaicin sensitive afferent nerves of rat urinary bladder. | |
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MedLine Citation:
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PMID: 21867704 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Nitro-oleic acid (9- and 10-nitro-octadeca-9-enoic acid, OA-NO(2)) is an electrophilic fatty acid nitroalkene derivative that modulates gene transcription and protein function via post-translational protein modification. Nitro-fatty acids are generated from unsaturated fatty acids by oxidative inflammatory reactions and acidic conditions in the presence of nitric oxide or nitrite. Nitroalkenes react with nucleophiles such as cysteine and histidine in a variety of susceptible proteins including transient receptor potential (TRP) channels in sensory neurons of the dorsal root and nodose ganglia. The present study revealed that OA-NO(2) activates TRP channels on afferent nerve terminals in the urinary bladder and thereby increases bladder activity. The TRPV1 agonist capsaicin (CAPS, 1 μM) and the TRPA1 agonist allyl isothiocyanate (AITC, 30 μM), elicited excitatory effects in bladder strips, increasing basal tone and amplitude of phasic bladder contractions (PBC). OA-NO(2) mimicked these effects in a concentration-dependent manner (1 μM-33 μM). The TRPA1 antagonist HC3-030031 (HC3, 30 μM) and the TRPV1 antagonist diaryl piperazine analog (DPA, 1 μM), reduced the effect of OA-NO(2) on phasic contraction amplitude and baseline tone. However, the non-selective TRP channel blocker, ruthenium red (30 μM) was a more effective inhibitor, reducing the effects of OA-NO(2) on basal tone by 75% and the effects on phasic amplitude by 85%. In bladder strips from CAPS-treated rats, the effect of OA-NO(2) on phasic contraction amplitude was reduced by 65% and the effect on basal tone was reduced by 60%. Pretreatment of bladder strips with a combination of neurokinin receptor antagonists (NK1 selective antagonist, CP 96345; NK2 selective antagonist, MEN 10,376; NK3 selective antagonist, SB 234,375, 1 μM each) reduced the effect of OA-NO(2) on basal tone, but not phasic contraction amplitude. These results indicate that nitroalkene fatty acid derivatives can activate TRP channels on CAPS-sensitive afferent nerve terminals, leading to increased bladder contractile activity. Nitrated fatty acids produced endogenously by the combination of fatty acids and oxides of nitrogen released from the urothelium and/or afferent nerves may play a role in modulating bladder activity. |
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Authors:
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D E Artim; F Bazely; S L Daugherty; A Sculptoreanu; K B Koronowski; F J Schopfer; S R Woodcock; B A Freeman; W C de Groat |
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Publication Detail:
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Type: In Vitro; Journal Article Date: 2011-08-16 |
Journal Detail:
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Title: Experimental neurology Volume: 232 ISSN: 1090-2430 ISO Abbreviation: Exp. Neurol. Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-10-10 Completed Date: 2011-12-07 Revised Date: 2012-04-23 |
Medline Journal Info:
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Nlm Unique ID: 0370712 Medline TA: Exp Neurol Country: United States |
Other Details:
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Languages: eng Pagination: 90-9 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Experimental Neurology, 200 Lothrop St., W1340 Biomedical Science Tower, Pittsburgh, PA 15260, USA. dea20@pitt.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Capsaicin / pharmacology Dose-Response Relationship, Drug Female Oleic Acid / pharmacology* Rats Rats, Sprague-Dawley Sensory Receptor Cells / drug effects* Sensory System Agents / pharmacology TRPV Cation Channels / agonists*, antagonists & inhibitors* Urinary Bladder / drug effects, innervation, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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R01 DK077783-04/DK/NIDDK NIH HHS; R37 DK049430-14/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Sensory System Agents; 0/TRPV Cation Channels; 112-80-1/Oleic Acid; 404-86-4/Capsaicin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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