The Deorphanization of TRPV1 and the Emergence of Octadecadienoids as a New Class of Lipid Transmitters

Flores, Christopher M.; Vasko, Michael R.

doi:10.1124/mi.10.3.4

Cited by 10 publications

(7 citation statements)

References 9 publications

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“…Original efforts to deorphanize TRPV1 channels [63] suggested that endocannabinoids, such as anandamide, were TRPV1 agonists [35]. Later, N-arachidonoyl-dopamine (NADA) and the N-oleyl-dopamine (OLDA) [38,60] were also determined to be TRPV1 agonists.…”

Section: Lipid Metabolites As Modulators Of Trp Channel Functionmentioning

confidence: 98%

TRP channels interaction with lipids and its implications in disease

Taberner

Fernández‐Ballester

Fernández-Carvajal

et al. 2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Transient receptor potential (TRP) proteins are a family of ion channels central for sensory signaling. These receptors and, in particular, those involved in thermal sensing are also involved in pain signaling. Noteworthy, thermosensory receptors are polymodal ion channels that respond to both physical and chemical stimuli, thus integrating different environmental clues. In addition, their activity is modulated by algesic agents and lipidergic substances that are primarily released in pathological states. Lipids and lipid-like molecules have been found that can directly activate some thermosensory channels or modulate their activity by either potentiating or inhibiting it. To date, more than 50 endogenous lipids that can regulate TRP channel activity in sensory neurons have been described, thus representing the majority of known endogenous TRP channel modulators. Lipid modulators of TRP channels comprise lipids from a variety of metabolic pathways, including metabolites of the cyclooxygenase, lipoxygenase and cytochrome-P450 pathways, phospholipids and lysophospholipids. Therefore, TRP-channels are able to integrate and interpret incoming signals from the different metabolic lipid pathways. Taken together, the large number of lipids that can activate, sensitize or inhibit neuronal TRP-channels highlights the pivotal role of these molecules in sensory biology as well as in pain transduction and perception. This article is part of a Special Issue entitled: Lipid-protein interactions. Guest Editors: Amitabha Chattopadhyay and Jean-Marie Ruysschaert.

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Section: Lipid Metabolites As Modulators Of Trp Channel Functionmentioning

confidence: 98%

TRP channels interaction with lipids and its implications in disease

Taberner

Fernández‐Ballester

Fernández-Carvajal

et al. 2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

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“…A number of putative endogenous TRPV1 agonists, with comparable efficacy to capsaicin, have been identified including anandamide (Smart et al, 2000), N-arachidonoyldopamine (Huang et al, 2002), 12-hydroperoxyeicosatetraenoic acid, 15-hydroperoxyeicosatetraenoic acid (Hwang et al, 2000;Flores and Vasko, 2010). Modulation of endogenous pro-nociceptive TRPV1 ligand generation, via manipulation of the enzymatic pathways that regulate their levels, (Starowicz et al, 2007) is an alternative approach by which TRPV1based analgesia could be developed.…”

Section: Introductionmentioning

confidence: 99%

The contribution of the endogenous TRPV1 ligands 9‐HODE and 13‐HODE to nociceptive processing and their role in peripheral inflammatory pain mechanisms

Alsalem

Wong

Millns

et al. 2013

British J Pharmacology

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Background and Purpose The transient receptor potential vanilloid type 1 (TRPV1) plays a fundamental role in the detection of heat and inflammatory pain responses. Here we investigated the contribution of two potential endogenous ligands [9‐ and 13‐ hydroxyoctadecadienoic acid (HODE)] to TRPV1‐mediated noxious responses and inflammatory pain responses. Experimental Approach 9‐ and 13‐HODE, and their precursor, linoleic acid, were measured in dorsal root ganglion (DRG) neurons and in the hindpaws of control and carrageenan‐inflamed rats by liquid chromatography/tandem electrospray mass spectrometry. Calcium imaging studies of DRG neurons were employed to determine the role of TRPV1 in mediating linoleic acid, 9‐HODE‐ and 13‐HODE‐evoked responses, and the contribution of 15‐lipoxygenase to the generation of the HODEs. Behavioural studies investigated the contribution of 9‐ and 13‐HODE and 15‐lipoxygenase to inflammatory pain behaviour. Key Results 9‐HODE (35 ± 7 pmol g−1) and 13‐HODE (32 ± 6 pmol g−1) were detected in hindpaw tissue, but were below the limits of detection in DRGs. Following exposure to linoleic acid, 9‐ and 13‐HODE were detected in DRGs and TRPV1 antagonist‐sensitive calcium responses evoked, which were blocked by the 15‐lipoxygenase inhibitor PD146176 and an anti‐13‐HODE antibody. Levels of linoleic acid were significantly increased in the carrageenan‐inflamed hindpaw (P < 0.05), whereas levels of 9‐ and 13‐HODE were, however, decreased. Intraplantar co‐administration of anti‐9‐ and 13‐HODE antibodies and treatment with PD146176 significantly (P < 0.01) attenuated carrageenan‐induced hyperalgesia. Conclusions and Implications This study demonstrates that, although 9‐ and 13‐HODE can activate TRPV1 in DRG cell bodies, the evidence for a role of these lipids as endogenous peripheral TRPV1 ligands in a model of inflammatory pain is at best equivocal.

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“…It is activated by capsaicin [1], noxious heat (>43°C), low pH (5.2) [1–3], voltage [4, 5], various lipids [2, 6–11], and other pungent compounds such as zingerone, piperine, and those found in garlic and onion, such as allicin [12]. Similar to other six-transmembrane domain channels, TRPV1 probably forms a tetrameric quaternary structure [13], where each subunit contributes to the ion-conducting pore and the selectivity filter.…”

Section: Partmentioning

confidence: 99%

Antioncogenic Effects of Transient Receptor Potential Vanilloid 1 in the Progression of Transitional Urothelial Cancer of Human Bladder

et al. 2012

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The progression of normal cells to a tumorigenic and metastatic state involves the accumulation of mutations in multiple key signaling proteins, encoded by oncogenes and tumor suppressor genes. Recently, members of the TRP channel family have been included in the oncogenic and tumor suppressor protein family. TRPM1, TRPM8, and TRPV6 are considered to be tumor suppressors and oncogenes in localized melanoma and prostate cancer, respectively. Herein, we focus our attention on the antioncogenic properties of TRPV1. Changes in TRPV1 expression occur during the development of transitional cell carcinoma (TCC) of human bladder. A progressive decrease in TRPV1 expression as the TCC stage increases triggers the development of a more aggressive gene phenotype and invasiveness. Finally, downregulation of TRPV1 represents a negative prognostic factor in TCC patients. The knowledge of the mechanism controlling TRPV1 expression might improve the diagnosis and new therapeutic strategies in bladder cancer.

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The Deorphanization of TRPV1 and the Emergence of Octadecadienoids as a New Class of Lipid Transmitters

Cited by 10 publications

References 9 publications

TRP channels interaction with lipids and its implications in disease

TRP channels interaction with lipids and its implications in disease

The contribution of the endogenous TRPV1 ligands 9‐HODE and 13‐HODE to nociceptive processing and their role in peripheral inflammatory pain mechanisms

Antioncogenic Effects of Transient Receptor Potential Vanilloid 1 in the Progression of Transitional Urothelial Cancer of Human Bladder

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