Erucamide as a Modulator of Water Balance: New Function of a Fatty Acid Amide

Hamberger, Anders; Stenhagen, Gunnar

doi:10.1023/a:1022364830421

Cited by 37 publications

(25 citation statements)

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“…[9][10][11] Similarly, erucamide has previously been reported to possess angiogenic and fluid homeostatic activity in vivo. 12,13 Accordingly, we next sought to determine whether we could demonstrate biological activity of erucamide and OEA at a common biological target. Commercially obtained samples of erucamide and OEA as well as the erucamide-containing DMSO extracts prepared from the 50-µL pipette tips were tested for the ability to stimulate cyclic AMP (cAMP) accumulation in cells expressing a G-protein-coupled receptor (GPCR) known to be activated by fatty acid ligands.…”

Section: Resultsmentioning

confidence: 99%

Extraction, Identification, and Functional Characterization of a Bioactive Substance From Automated Compound-Handling Plastic Tips

Watson¹,

Greenough²,

Leet³

et al. 2009

SLAS Discovery

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Disposable plastic labware is ubiquitous in contemporary pharmaceutical research laboratories. Plastic labware is routinely used for chemical compound storage and during automated liquid-handling processes that support assay development, high-throughput screening, structure-activity determinations, and liability profiling. However, there is little information available in the literature on the contaminants released from plastic labware upon DMSO exposure and their resultant effects on specific biological assays. The authors report here the extraction, by simple DMSO washing, of a biologically active substance from one particular size of disposable plastic tips used in automated compound handling. The active contaminant was identified as erucamide ((Z)-docos-13-enamide), a long-chain mono-unsaturated fatty acid amide commonly used in plastics manufacturing, by gas chromatography/mass spectroscopy analysis of the DMSO-extracted material. Tip extracts prepared in DMSO, as well as a commercially obtained sample of erucamide, were active in a functional bioassay of a known G-protein-coupled fatty acid receptor. A sample of a different disposable tip product from the same vendor did not release detectable erucamide following solvent extraction, and DMSO extracts prepared from this product were inactive in the receptor functional assay. These results demonstrate that solvent-extractable contaminants from some plastic labware used in the contemporary pharmaceutical research and development (R&D) environment can be introduced into physical and biological assays during routine compound management liquid-handling processes. These contaminants may further possess biological activity and are therefore a potential source of assay-specific confounding artifacts.

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Section: Resultsmentioning

confidence: 99%

Extraction, Identification, and Functional Characterization of a Bioactive Substance From Automated Compound-Handling Plastic Tips

Watson¹,

Greenough²,

Leet³

et al. 2009

SLAS Discovery

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“…Fatty acids were dissolved in ethanol, converted to the sodium salt with excess NaOH, dried under vacuum, and then dissolved in phosphate-buffered saline (PBS) to make a 25 mM solution. The sample was then heated in 49°C water bath for 5 min before angiogenesis ( 25 ) and controls water balance ( 26 ). In addition, both mammalian phospholipase A 2 (PLA 2 ) and epoxide hydrolase (EH) are inhibited by series of PFAMs, with arachidonamide and ␥ -linolenamide being the most potent for the inhibition of PLA 2 ( 27 ) and elaidamide being the most potent for the inhibition of EH ( 28 ).…”

Section: Use Of Bsa As a Fatty Acid Carriermentioning

confidence: 99%

Primary fatty acid amide metabolism: conversion of fatty acids and an ethanolamine in N18TG2 and SCP cells

Farrell¹,

Chen

Barazanji

et al. 2012

Journal of Lipid Research

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ceramides and sphingolipids ( 1, 2 ). Primary fatty acid amides (PFAM), R-CO-NH 2 with R being a long-chain fatty acid, were fi rst identifi ed from a biological source in 1989 with the identifi cation of palmitamide, palmitoleamide, oleamide, elaidamide, and linoleamide in luteal phase plasma ( 3 ). At the time of their discovery, the biological function of these mammalian PFAMs was unknown. Interest in the PFAMs dramatically intensifi ed with the discoveries that oleamide accumulated in the cerebrospinal fl uid (CSF) of sleep-deprived cats, that it is a natural component of the CSF in the cat, rat, and human, and that the administration of synthetic oleamide induced physiological sleep in rats ( 4 ). Intriguingly, later studies found that oleamide levels in the brain of the ground squirrel were ‫ف‬ 2.5-fold higher in hibernating animals relative to those found in nonhibernating animals ( 5 ). Other functions ascribed to oleamide, since its discovery as a sleep-inducing PFAM, include the ability to modulate gap junction communication in glial cells ( 6, 7 ), tracheal epithelial cells ( 8 ), seminiferous tubule cells ( 9 ), and fi broblasts ( 10 ); to allosterically activate the GABA A receptors and specifi c subtypes of the serotonin receptor ( 11-13 ); to affect memory processes ( 14 ); to increase food intake ( 15 ); to reduce anxiety and pain ( 16,17 ); to depress body temperature and locomotor activity ( 17,18 ); to stimulate Ca(II) release ( 19 ); and to relax blood vessels ( 20,21 ).Although much of the research regarding the PFAMs has focused on oleamide, studies show that some of the other known PFAMs are bioactive. Palmitamide is weakly anticonvulsant ( 22 ); linoleamide regulates Ca(II) fl ux ( 23 ) and inhibits the erg current ( 24 ); and erucamide stimulates Abstract Primary fatty acid amides (PFAM) are important signaling molecules in the mammalian nervous system, binding to many drug receptors and demonstrating control over sleep, locomotion, angiogenesis, and many other processes. Oleamide is the best-studied of the primary fatty acid amides, whereas the other known PFAMs are signifi cantly less studied. Herein, quantitative assays were used to examine the endogenous amounts of a panel of PFAMs, as well as the amounts produced after incubation of mouse neuroblastoma N 18 TG 2 and sheep choroid plexus (SCP) cells with the corresponding fatty acids or N -tridecanoylethanolamine. Although fi ve endogenous primary amides were discovered in the N 18 TG 2 and SCP cells, a different pattern of relative amounts were found between the two cell lines. Higher amounts of primary amides were found in SCP cells, and the conversion of N -tridecanoylethanolamine to tridecanamide was observed in the two cell lines. The data reported here show that the N 18 TG 2 and SCP cells are excellent model systems for the study of PFAM metabolism. Furthermore, the data support a role for the N -acylethanolamines as precursors for the PFAMs and provide valuable new kinetic results useful in modeling the metabolic fl ux throug...

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“…[96,97] for reviews]. Like oleamide, other members of the PFAM are bioactive: linoleamide increases Ca 2+ flux [98] and inhibits the erg current in pituitary cells [99], erucamide stimulates the growth of blood vessels [100] and regulates fluid imbalance [101] and elaidamide might function as an endogenous inhibitor of epoxide hydrolase [102].…”

Section: Primary Fatty Acid Amidesmentioning

confidence: 99%

Biosynthesis, degradation and pharmacological importance of the fatty acid amides

Farrell

Merkler

2008

Drug Discovery Today

117

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The identification of two biologically active fatty acid amides, N-arachidonoylethanolamine (anandamide) and oleamide, has generated a great deal of excitement and stimulated considerable research. However, anandamide and oleamide are merely the best-known and best-understood members of a much larger family of biologically-occurring fatty acid amides. In this review, we will outline which fatty acid amides have been isolated from mammalian sources, detail what is known about how these molecules are made and degraded in vivo, and highlight their potential for the development of novel therapeutics. Keywords N-acylamino acid; N-acyldopamine; N-acylethanolamine; primary fatty acid amide; N-acylamideThe fatty acid amide bond has long been recognized in nature, being important in the structure of the ceramides [1] and the sphingolipids [2]. The first non-sphingosine based fatty acid amide isolated from a natural source was N-palmitoylethanolamine from egg yolk in 1957 [3]. Interest in the N-acylethanolamines (NAEs) dramatically increased upon the identification of Narachidonoylethanolamine (anandamide) as the endogenous ligand for the cannabinoid receptors in the mammalian brain [4]. It is now known that a family of NAEs is found in the brain and in other tissues [5,6].In addition to the NAEs, other classes of fatty acid amides have been characterized, namely the N-acylamino acids (NAAs) [7], the N-acyldopamines (NADAs) [8] and the primary fatty acid amides (PFAMs) [9,10] (Figure 1). Relative to NAEs, much less is currently known about the NAAs, the NADAs and the PFAMs, except that they are found in biological systems. The goal of this review is to summarize the current state of knowledge regarding the different classes of endogenous fatty acid amides and highlight their potential for drug discovery (see refs. [11-13] for earlier reviews) © 2008 Elsevier Ltd. All rights reserved.Corresponding author: Merkler, D.J (E-mail: merkler@cas.usf.edu) phone 813-974-3579; fax 813-974-1733. 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.Teaser SentenceFatty acid amides are a family of mammalian bioactive compounds. These molecules and the enzymes involved in their metabolism provide an opportunity to develop new drugs to treat human disease. -palmitoyl-, N-stearoyl-and N-oleoylethanolamine [5,11], each compromising ≥25% of total brain NAEs. Other less abundant NAEs found in the brain are anandamide, N-linoleoyl-, N-linolenoyl-, N-dihomo-γ-linolenoyl-and N-docosatetraenoylethanolamine [11]. In addition to the brain, the NAEs are widespread in the peripheral tissues [5]. The mos...

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Erucamide as a Modulator of Water Balance: New Function of a Fatty Acid Amide

Cited by 37 publications

References 50 publications

Extraction, Identification, and Functional Characterization of a Bioactive Substance From Automated Compound-Handling Plastic Tips

Extraction, Identification, and Functional Characterization of a Bioactive Substance From Automated Compound-Handling Plastic Tips

Primary fatty acid amide metabolism: conversion of fatty acids and an ethanolamine in N18TG2 and SCP cells

Biosynthesis, degradation and pharmacological importance of the fatty acid amides

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