The expanding field of cannabimimetic and related lipid mediators

Bradshaw, Heather B.; Walker, J. Michael

doi:10.1038/sj.bjp.0706093

Cited by 146 publications

(151 citation statements)

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“…The lipoamino acids and endovanilloids exhibit interesting biological activities [42,43]. A few targets of the lipoamino acids and endovanilloids have been identified, but for the most part, their mechanisms of action and regulation remain unclear.…”

Section: Discussionmentioning

confidence: 99%

Oxidative metabolism of lipoamino acids and vanilloids by lipoxygenases and cyclooxygenases

Prusakiewicz¹,

Turman²,

Vila³

et al. 2007

Archives of Biochemistry and Biophysics

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The lipoamino acids and endovanilloids have multiple roles in nociception, pain, and inflammation, yet their biological reactivity has not been fully characterized. Cyclooxygenases (COXs) and lipoxygenases (LOs) oxygenate polyunsaturated fatty acids to generate signaling molecules. The ability of COXs and LOs to oxygenate arachidonyl-derived lipoamino acids and vanilloids was investigated. COX-1 and COX-2 were able to minimally metabolize many of these species. However, the lipoamino acids were efficiently oxygenated by 12S-and 15S-LOs. The kinetics and products of oxygenation by LOs were characterized. Whereas 15S-LOs retained positional specificity of oxygenation with these novel substrates, platelet-type 12S-LO acted as a 12/15-LO. Fatty acid oxygenases may play an important role in the metabolic inactivation of lipoaminoacids or vanilloids or may convert them to bioactive derivatives.

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Section: Discussionmentioning

confidence: 99%

Oxidative metabolism of lipoamino acids and vanilloids by lipoxygenases and cyclooxygenases

Prusakiewicz¹,

Turman²,

Vila³

et al. 2007

Archives of Biochemistry and Biophysics

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“…Other amino acid conjugates have been found in diverse tissues (Bradshaw and Walker, 2005), for example, N-arachidonoyl-L-serine has recently been isolated from rat tissues (Bradshaw, 2005) and from bovine brain and reported to have vasodilatory effects in rat mesenteric arteries (Milman et al, 2006).…”

Section: Nih Public Accessmentioning

confidence: 99%

“…NAGly has been suggested to be the endogenous ligand for orphan G-proteincoupled receptor GPR18 based on preliminary data (Kohno et al, 2006;Samuelson et al, 1996). Like anandamide, NAGly is also a substrate for COX-2 giving rise to amino acid conjugates of the prostaglandins (Prusakiewicz et al, 2002).Other amino acid conjugates have been found in diverse tissues (Bradshaw and Walker, 2005), for example, N-arachidonoyl-L-serine has recently been isolated from rat tissues (Bradshaw, 2005) and from bovine brain and reported to have vasodilatory effects in rat mesenteric arteries (Milman et al, 2006).The origin of EMA-1 (20:4) has been a subject of interest for some time. Early observations raised the possibility that anandamide might be a precursor, which by an oxidative process could lead to EMA-1 (20:4) synthesis (Burstein et al, 2000).…”

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confidence: 99%

The elmiric acids: Biologically active anandamide analogs

Burstein

2008

Neuropharmacology

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SummaryAs chemical entities, lipoamino acids have been known for some time. However, more recently their occurrence and importance in mammalian species has been discovered. They appear to have close relationships with the endocannabinoids not only structurally but also in terms of biological actions. The latter include analgesia, anti-inflammatory effects, inhibition of cell proliferation and calcium ion mobilization. To date about 40 naturally occurring members of this family have been identified and, additionally, several synthetic analogs have been prepared and studied. To facilitate their identity, a nomenclature system has been suggested based on the name elmiric acid (EMA). The prototypic example, N-arachidonoyl glycine does not bind to CB1, however it does inhibit the glycine transporter GLYT2a and also appears to be a ligand for the orphan G-protein-coupled receptor GPR18. It may also have a role in regulating tissue levels of anandamide by virtue of its inhibitory effect on FAAH the enzyme that mediates inactivation of anandamide. Its concentration in rat brain is several fold higher than anandamide supporting its possible role as a physiological mediator. Future studies should be aimed at elucidating the actions of all of the members of this interesting family of molecules. Keywordsendocannabinoid; lipoamino acid; eicosanoid; elmiric acid; inflammation; anandamide Lipoamino acids (fatty acid-amino acid conjugates): general considerationsThe older literature on this topic is mainly concerned with lipoamino acids of bacterial origin (Batrakov et al., 2000;Kawai et al., 1990;Kawazoe et al., 1991;Lerouge et al., 1988;Miyazaki et al., 1993). These involve amino acid conjugation with complex and unusual fatty acids and little is known about their function in bacteria.More recently, attention has been given to lipoamino acids present in mammalian species in part because of their possible relationships to the endocannabinoids. The closely related analog of anandamide, N-arachidonylglycine (NAGly), is in a sense, a comparable acid analog to anandamide as the THC metabolite, THC-11-oic acid is to THC. NAGly is an endogenous substance found in rat brain and other sites that occurs in amounts greater than the closely related endocannabinoid, anandamide (Huang et al., 2001). However, the origin of NAGly in vivo is not completely understood. Sumner.Burstein@umassmed.edu, Tel: 508-856-2850, Fax: 508-856-2003. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Prior reports (Burstein et al. 1997;Huang et al., 2001), suggest that NAGly might have analgesic properties similar to tho...

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“…All mice were accustomed to the pain test conditions for 5 days before the experiments. The hot plate test was conducted before and repeated at 2,4,7,14,21,28,35,42,49,56, 63 days after intraplantar injection of RTX or saline.…”

Section: Hot Plate Testmentioning

confidence: 99%

Ablation and Regeneration of Peripheral and Central TRPV1 Expressing Nerve Terminals and the Consequence of Nociception

Yu¹,

Premkumar²

2015

TOPAINJ

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Transient Receptor Potential Vanilloid 1 (TRPV1) expressed in peripheral terminals is responsible for transducing thermal and chemical nociception. Role of TRPV1 expressed in the central terminals is not clear, however, its activation modulates synaptic transmission and contributes to central sensitization. In this study, we have determined the role of TRPV1 expressed in the peripheral and central terminals using resiniferatoxin (RTX), a potent TRPV1 agonist. A single intraplantar injection of RTX, within two days induced loss of capsaicin-induced nocifensive behavior and enhanced response latency to hot plate, which recovered over a period of two months. RTX treatment resulted in the ablation of peripheral TRPV1 expressing fibers in paw skin, which regenerated over the same time period. On the other hand, a single dose of intrathecal administration of RTX, within two days caused thermal hypoalgesia. RTX treatment ablated TRPV1 expressing central sensory nerve terminals. Intriguingly, in contrast to peripheral nerve terminal regeneration that occurred within two months, the central TRPV1 expressing nerve terminals did not regenerate even after five months. The present study demonstrates that TRPV1 in the peripheral and central terminals play a role in nociception and the peripheral terminals have the ability to regenerate, whereas the central terminals do not regenerate even after five months.

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The expanding field of cannabimimetic and related lipid mediators

Cited by 146 publications

References 74 publications

Oxidative metabolism of lipoamino acids and vanilloids by lipoxygenases and cyclooxygenases

Oxidative metabolism of lipoamino acids and vanilloids by lipoxygenases and cyclooxygenases

The elmiric acids: Biologically active anandamide analogs

Ablation and Regeneration of Peripheral and Central TRPV1 Expressing Nerve Terminals and the Consequence of Nociception

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