Oleamide Research Articles

Metabolic biomarker signature for predicting the effect of neoadjuvant chemotherapy of breast cancer.

The effect of breast cancer neoadjuvant chemotherapy (NCT) is strongly associated with breast cancer long term survival, especially when patients get a pathological complete response (PCR). It always is still unknown which patient is the potential one to get a PCR in the NCT. Thus, we have seeded blood-derived metabolite biomarkers to predict the effect of NCT of breast cancer. Patients who received either 6 or 8 cycles of anthracycline-docetaxel-based NCT (EC-T or TEC) had been assessed their response to chemotherapy-partial response (PR) (n=19) and stable disease (SD) (n=16). The serum samples had been collected before and after chemotherapy. Sixty-nine subjects were prospectively recruited with PR and SD patients before and after chemotherapy separately. Metabolomics profiles of serum samples were generated from 3,461 metabolites identified by liquid chromatography-mass spectrometry (LC-MS). Based on LC-MS metabolic profiling methods, nine metabolites were identified in this study: prostaglandin C1, ricinoleic acid, oleic acid amide, ethyl docosahexaenoic, hulupapeptide, lysophosphatidylethanolamine 0:0/22:4, cysteinyl-lysine, methacholine, and vitamin K2, which were used to make up a receiver operating characteristics (ROC) curve, a model for predicting chemotherapy response. With an area under the curve (AUC) of 0.957, the model has a specificity of 100% and sensitivity of 81.2% for predicting the response of PR and SD of breast cancer patients. A model with such good predictability would undoubtedly verify that the serum-derived metabolites be used for predicting the effect of breast cancer NCT. However, how identified metabolites work for prediction is still to be clearly understood.

Co-intercalation of organic cations/amide molecules into montmorillonite with tunable hydrophobicity and swellability

Organo-montmorillonite (OMt) has been widely used in paints, drilling fluids, clay/polymer nanocomposites, adsorbents and biosensors, however the full potential of OMt is yet to be discovered. The co-introduction of cationic and nonionic species into Mt has great potential to expand modification strategies and applications of Mt However, details regarding the intercalation mechanism of dual organic species remain unclear and the aspects of hydrophobicity and swellability of OMt are unknown. In this work, the co-introduction into OMt of octadecyltrimethylammonium (ODTMA+) cations and a nonionic specie erucamide (EA), and ODTMA+ with an oleamide (OA). was investigated. The resultant OMt samples were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric analysis and scanning electron microscopy. Hydrophobicity and swellability of the OMt were examined. The results showed that neither EA nor OA could be effectively introduced into the interlayer spaces of Mt, although adsorption of EA and OA onto the external surface of Mt did occur. In the presence of ODTMA+, however, both EA and OA were successfully co-intercalated into the interlayer spaces of Mt, and the basal spacing (d001) of ODTMA+, EA and OA co-intercalated OMt increased to as much as 4.2 nm. Such dual modification appeared to be effective at tailoring hydrophobicity. The swellability of ODTMA+, EA and OA co-intercalated OMt in xylene increased with the increase in the amount of EA and OA loaded. When Mt was modified using 1.0 CEC ODTMA+ with 0.5–1.75 CEC EA, 0.2 g OMt in 10 mL xylene swelled to take 10 ml volume, equating to a swell index of 100%. Here, a two-stage intercalation is proposed: cationic exchange of ODTMA+ to form a paraffin-type monolayer, followed by hydrophobic entropy-driven adsorption of nonionic EA and OA by intertwining organic chains into the interlayer spaces of the OMt The findings show the promise of co-intercalation to introduce many other cations and nonionic organic species into the interlayer spaces of Mt, and thus greatly expands the types of OMt for new applications.

Research on Oleic Acid Amide Betaine Used in Surfactant‐Polymer Compound Flooding for Ordinary Heavy Oil

AbstractIn view of the low recovery rate associated with water flooding, as well as the scaling problems caused by traditional alkali‐surfactant‐polymer flooding, the feasibility of using a betaine surfactant with high interfacial activity for chemical flooding of ordinary heavy oil was investigated. Aqueous solutions of oleic acid amide betaine (OAAB) with the mass concentration of 0.01% can reduce the oil–water interfacial tension to the ultralow level (10−3 mN m−1), making it suitable for chemical flooding. To solve the problem of high adsorption onto sandstone, static adsorption tests and dynamic adsorption tests were carried out. The results show that the weakly alkaline lignin can significantly reduce the adsorption quantity of OAAB by more than 40%, based on which, a compound‐flooding system of 0.1% partially hydrolyzed polyacrylamide (HPAM) + 0.1% OAAB +0.75% lignin was constructed. Compared with water flooding, the ultimate rate was enhanced by 20.4%, resulting in a final recovery rate of 53.9%. The study of oil displacement mechanism shows that the excellent ability to reduce the oil–water interfacial tension of OAAB can emulsify heavy oil to small droplets easily, exhibiting better capacity in oil displacement efficiency. The polymer can increase the viscosity of the aqueous phase, reduce the mobility ratio of water to oil, weaken the fingering effect, and improve the sweep efficiency. Lignin can not only reduce the adsorption quantity of betaine surfactant, but also promote the adsorption of OAAB onto the oil–water interface, leading to enhance the emulsification performance of OAAB and maintain the oil displacement efficiency effectively. Therefore, the surfactant‐polymer flooding system based on the betaine surfactant can be developed into an economically and technically feasible flooding technology suitable for ordinary heavy oil reservoirs.

Modulation of the Endocannabinoid System as a Potential Anticancer Strategy.

Currently, the involvement of the endocannabinoid system in cancer development and possible options for a cancer-regressive effect of cannabinoids are controversially discussed. In recent decades, a number of preclinical studies have shown that cannabinoids have an anticarcinogenic potential. Therefore, especially against the background of several legal simplifications with regard to the clinical application of cannabinoid-based drugs, an extended basic knowledge about the complex network of the individual components of the endocannabinoid system is required. The canonical endocannabinoid system consists of the endocannabinoids N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol as well as the Gi/o protein-coupled transmembrane cannabinoid receptors CB1 and CB2. As a result of extensive studies on the broader effect of these factors, other fatty acid derivatives, transmembrane and intracellular receptors, enzymes and lipid transporters have been identified that contribute to the effect of endocannabinoids when defined in the broad sense as “extended endocannabinoid system.” Among these additional components, the endocannabinoid-degrading enzymes fatty acid amide hydrolase and monoacylglycerol lipase, lipid transport proteins of the fatty acid-binding protein family, additional cannabinoid-activated G protein-coupled receptors such as GPR55, members of the transient receptor family, and peroxisome proliferator-activated receptors were identified as targets for possible strategies to combat cancer progression. Other endocannabinoid-related fatty acids such as 2-arachidonoyl glyceryl ether, O-arachidonoylethanolamine, N-arachidonoyldopamine and oleic acid amide showed an effect via cannabinoid receptors, while other compounds such as endocannabinoid-like substances exert a permissive action on endocannabinoid effects and act via alternative intracellular target structures. This review gives an overview of the modulation of the extended endocannabinoid system using the example of anticancer cannabinoid effects, which have been described in detail in preclinical studies.

Comparison of the Composition of Three Mahonia Plants Based on GC-MS Analysis

Plant material evidence inspection is Mahonia bealei (Fort.) Carr., Mahonia fortunei (Lindl.) and Mahonia bodinieri Gagnep. are three common medicinal plants commonly found in Mahonia. In this study, gas chromatography-mass spectrometry (GC-MS) was used to compare the chemical constituents of stems and leaves of these three plants. The results showed that 6 of the volatile oils of the three plant species contained the same chemical composition, which was neophytadiene, palmitic acid, n-dodecane, octacosane, erucamide, and vitamin E oil, but the percentage content was difference. The main components of the volatile oils of the three plant stems were different. Erucamide was only detected in Mahonia fortunei (Lindl.) Fedde, oleic acid amide only detected in Mahonia bealei (Fort.) Carr. , and oxidized cyclooctene , and four compounds such as triphenylphosphine oxide was detected in Mahonia bodinieri Gagnep. ..

Controlled Synthesis of Hierarchical Pd Nanodendrites and Their Electrocatalytic Properties.

Well-defined hierarchical Pd nanodendrites with (111) surface were successfully synthesized with Pd(acac)2 as a precursor, polyvinylpyrrolidone (PVP) as a stabilizer, CO as a reducing agent in the presence of appropriate amounts of NaAc and oleylamide (OAm) at 100 °C for 3 h under atmospheric pressure. OAm played an important role in controlling the growth of the hierarchical dendritic nanostructures of the final products. The formation of the hierarchical Pd dendrites was ascribed to the OAm-confined growth from the tips along 〈111〉 axis directions. This kind of hierarchical Pd nanodendrites exhibited an enhanced electrocatalytic activity for the electro-oxidation of formic acid compared with Pd black.

Flotation mechanism of oleic acid amide on apatite

In this study, a new collector for apatite flotation was synthesized by a series of reactions, including sulfation and amidation, using sodium oleate as raw material. An investigation on flotation behavior and mechanism of oleic acid amide onto apatite was carried out by micro flotation tests, zeta potential measurements, and XPS analysis. The flotation results showed that mixing sodium oleate and oleic acid amide could float apatite well in a pH 7.5–9.5 range even at the acid number of 120mgKOH/g and it exhibits better collecting capacity on apatite than sodium oleate collector. The XPS analysis data correlated with zeta potential showed that: the zeta potential of apatite become more negatively charged under neighborhood pH=8.5 and the oleic ions (C17H33COO−, (C17H33COO)22− and C17H33CONH−) in the mixing collector suspension can get chemisorbed by CaO bond formation on the apatite surface, also the moleculars (C17H33CONH2) and micelles (C17H33CONH2)m in oleic acid amide can get chemisorbed on the apatite surface by CaO or CaN bond formation.

Anti-angiogenesis therapy and gap junction inhibition reduce MDA-MB-231 breast cancer cell invasion and metastasis in vitro and in vivo.

Cancer cells secrete VEGF, which plays a key role in their growth, invasion, extravasation and metastasis. Direct cancer cell-endothelial cell interaction, mediated by gap junctions, is of critical importance in the extravasation process. In this study, we evaluated avastin (Av), an anti-VEGF antibody; and oleamide (OL), a gap junction inhibitor, using MDA-MB-231 human breast cancer cells in vitro and a xenograft murine model in vivo. Results showed that Av/OL significantly decreased proliferation, induced cell cycle arrest and decreased migration and invasion of MDA-MB-231 cells in vitro. In addition, Av/OL significantly decreased homo and hetero-cellular communication interaction between MDA-MDA and MDA-endothelial cells, respectively. The expression levels of several factors including VEGF, HIF1α, CXCR4, Cx26, Cx43, and MMP9 were attenuated upon Av/OL treatment in vitro. On the other hand, avastin, but not oleamide, reduced tumor size of NSG mice injected subdermally (s.d.) with MDA-MB-231 cells, which was also associated with increased survival. Furthermore, Av but also OL, separately, significantly increased the survival rate, and reduced pulmonary and hepatic metastatic foci, of intravenously (i.v.) injected mice. Finally, OL reduced MMP9 protein expression levels, better than Av and in comparisons to control, in the lungs of MDA-MB-231 i.v. injected NSG mice. In conclusion, while avastin has anti-angiogenic, anti-tumor and anti-metastatic activities, oleamide has anti-metastatic activity, presumably at the extravasation level, providing further evidence for the role of gap junction intercellular communication (GJIC) in cancer cell extravasation.

Atmospheric Pressure Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry of Friction Modifier Additives Analyzed Directly from Base Oil Solutions

To develop new products and to apply measures of quality control quick and simple accessibility of additive composition in automotive lubrication is important. The aim of this study was to investigate the possibility of analyzing organic friction modifier additives by means of atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry (AP-MALDI-MS) from lubricant solutions without the use of additional separation techniques. Analyses of selected friction modifier ethoxylated tallow amines and oleic acid amide were compared using two ionization methods, positive-ion electrospray ionization (ESI) and AP-MALDI, using a LTQ Orbitrap mass spectrometer. Pure additives were characterized from solvent solutions, as well as from synthetic and mineral base oil mixtures. Detected ions of pure additive samples consisted mainly of [M + H]+, but also alkali metal adducts [M + Na]+ and [M + K]+ could be seen. Characterizations of blends of both friction modifiers from the base oil mixtures were carried out as well and showed significant intensities for several additive peaks. Thus, this work shows a method to directly analyze friction modifier additives used in the automotive industry from an oil blend via the use of AP-MALDI without any further separation steps. The method presented will further simplify the acquisition of data on lubricant composition and additives. Furthermore, it allows the perspective of analyzing additive reaction products directly from formulated oil blends.

Effect of gap junction-mediated intercellular communication on growth differentiation factor 5-induced chondrogenic differentiation in vitro

Objective To investigate the effect of gap junctional blocker oleamide on growth differentiation factor 5 (GDF-5) induced chondrogenic differentiation.Methods hunan mesenchymal stem cells (hMSCs) were isolated and cultured in vitro,and the cells from Passage 3 were used in this study.hMSCs were randomly grouped into three according to the kinds of induction medium (0,100 μg/L GDF-5,100 μg/L GDF-5 + 2.5 μmol/L oleamide).The proliferation of hMSCs was investigated by methyl thiazol tetrazolium (MTT) assay.The cells were resuspended and the pellets were constructed by centrifugation at a density of 5 × 109/L,and then continued to be kept for two weeks.Reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect the expression of mRNA of type Ⅱ collagen,comexin 43 (Cx43)and aggrecan.Western blotting was performed to detect the expression of protein of type Ⅱ collagen,Cx43and aggrecan.Toluidine blue was performed to detect extracellular matrix staining.Results GDF-5 can promote the mRNA expression of type Ⅱ collagen,Cx43 and aggrecan (1.00 ± 0.03 vs.0.40 ± 0.12 ;1.00 ±0.07 vs.0.32 ±0.02; 1.00 ±0.02 vs.0.45 ±0.01,P ＜0.01),and the relative protein expression was also increased (1.50±0.11 vs.0.53 ±0.07; 1.70 ±0.14 vs.0.52 ±0.04; 1.00 ±0.12 vs.0.50±0.06,P＜0.01).While oleamide could up-regulate the expression of mRNA of Cx43 (0.94 ±0.12 vs.0.45 ±0.01,P ＜0.01),but had no effect on type Ⅱ collagen and aggrecan mRNA expression.Oleamide could down-regulate the expression of protein of type Ⅱ collagen and aggrecan,but had no effect onCx43 protein expression(0.42 ± 0.04 vs.0.53 ±0.07; 0.38 ±0.06 vs.0.52 ±0.04,P＜0.01).Toluidine blue staining showed that GDF-5 can promote the synthesis of aggrecan.Conclusion GDF-5 modulation of chondrogenesis involves gap junction-mediated intercellular communication. Key words: Chondrogenic differentiation ; Growth differentiation factor 5 ; Oleamide ; Comexin 43

Improved soiling resistance of polypropylene fibers on the addition of synthetic compounds

With the aim of enhancing the soil resistance of polypropylene (PP) fibers, polydimethylsiloxane (PDMS) and/or oleamide (OA) were added, and the soiling and wear resistances of the obtained fibers were evaluated. Films made from PP with the addition of PDMS and/or OA were fabricated and their water repellencies were evaluated by using droplets to measure their contact angles. The water contact angle increased with increasing amount of PDMS and/or OA added to PP. These blended resins were then used to produce fibers, which were in turn used to form fabrics. The soil resistances of these fabrics were evaluated by immersing them in aqueous solutions of a water-soluble artificial soiling substance for 1 min. Fiber G, for which both PDMS and OA had been added to PP, had a soiling ratio that was about 8–15% lower than that of pure PP fibers to which nothing had been added. Longer immersion of 24 h resulted in Fiber E, for which only PDMS had been added, having the lowest soiling ratio. In contrast, Fibers L and G (produced by adding OA) had relatively high soiling ratios when immersed for a long time. The wear resistances of knitted fabrics were evaluated using an abrasion tester. Fabric made from pure PP fibers had holes after 20 cycles of abrasion, whereas fabrics formed from fibers to which PDMS and/or OA had been added did not have holes even after 100 cycles of abrasion, which represents a remarkable improvement in wear resistance.

Oleamide and Oleamide–Lipid Mixed Monolayers

Oleamide (OA) and its mixtures with other lipids are of interest in some biological systems, such as the tear film or the cerebrospinal fluid. In this work, the behavior of OA, OA–dipalmitoylphospatidylcholine (DPPC), and OA–cholesterol films is studied using surface pressure–area isotherms and atomic force microscopy, and analyzing the collapse pressure vs. composition, the compressibility, and the mean area vs. composition for several surface pressures. It is observed that OA forms homogeneous monolayers in a liquid-expanded state until the collapse surface pressure and the mixing with DPPC and cholesterol. The collapse surface pressure changes with the mixture composition, and in the case of DPPC, a noticeable influence of OA in the liquid-expanded/liquid-condensed phase change of DPPC is observed. The excess area is positive for the OA/DPPC films, but mostly negative for the OA–cholesterol films. These results are of interest for the target of formulation of artificial tears containing lipids.

Application of a SCC-DFTB QM/MM approach to the investigation of the catalytic mechanism of fatty acid amide hydrolase

Self-consistent charge density functional tight binding (SCC-DFTB) is a promising method for hybrid quantum mechanics/molecular mechanics (QM/MM) simulations of enzyme-catalyzed reactions. The acylation reaction of fatty acid amide hydrolase (FAAH), a promising drug target, was investigated by applying a SCC-DFTB/CHARMM27 scheme. Calculated potential energy barriers resulted in reasonable agreement with experiments for oleamide (OA) and oleoylmethyl ester (OME) substrates, outperforming previous calculations performed at the PM3/CHARMM22 level. Furthermore, the experimental preference of FAAH in hydrolyzing OA faster than OME was adequately reproduced by calculations. All these findings indicate that the SCC-DFTB/CHARMM27 approach can be successfully applied to mechanistic investigations of FAAH-catalyzed reactions.

Characterization of a Synechocystis sp. from Egypt with the potential of bioactive compounds production

A polyphasic approach was employed to describe a unicellular coccoid cyanobacterium isolated from Terraat El Khashab, Helwan, Egypt. The cells were characterised by their small diameter (1.9–2.2 μm) and lack of buoyancy. The cultures grew best at a temperature range of 20–40°C and moderate light intensity (20–50 μmol photon m−2 s−1). To verify its cyanobacterial nature, sequencing of 16S rRNA gene using cyanobacterial specific primers was performed followed by a phylogenetic analysis. The sequence best-matched Synechocystis sp. PCC6803 with 90% similarity. The phylogenetic analysis placed the isolate within a major clade containing different Synechocystis isolates. The fatty acid composition was rich in saturated fatty acids while polyunsaturated fatty acids were scarce. The phytochemical screening revealed the presence of flavenoids, alkaloids and saponins and absence of tannins. Vitamin C was also present in a considerable quantity. Some of the lipophilic fractions showed antimicrobial bioactivity against several pathogens. The pure bioactive compound from highest bioactive fraction was identified as oleic acid amide (M.wt.281) using chemical analyses including FT/IR, UV, proton H-NMR and GC-mass. The study highlights the importance of investigating the biotechnological potential of microorganisms inhabiting unusual niches.

Lipids of human meibum: mass-spectrometric analysis and structural elucidation

The purpose of this study was to structurally characterize the major lipid species present in human meibomian gland secretions (MGS) of individual subjects by means of ion trap atmospheric pressure ionization mass spectrometry analysis (API MS(n)). The samples of MGS and authentic lipid standards were analyzed in direct infusion and high-pressure liquid chromatography (HPLC) experiments with API MS(n) detection of the analytes (HPLC API MS(n)). The major precursor ions were isolated and subjected to further sequential fragmentation in MS(n) experiments, and their fragmentation patterns were compared with those of authentic lipid standards. Multiple precursor ions were observed in the positive-ion mode. Among those, previously identified cholesterol (Chl; m/z 369; [M - H(2)O + H](+)) and oleic acid (OA; m/z 283; [M + H](+)) were found. The other major compounds of the general molecular formula C(n)H(2n-2)O(2) were consistent with wax esters (WEs), with OA as fatty acyl component. Accompanying them were two homologous series of compounds that fit the molecular formulas C(n)H(2n-4)O(2) and C(n)H(2n)O(2). Subset 2 was found to be a homolog series of linoleic acid-based WEs, whereas subset 3 was, apparently, a mixture of stearic acid-based WEs. HPLC API MS(n) analysis revealed the presence of large quantities of cholesteryl esters (Chl-Es) in all of the tested samples. Less than 0.1% (w/w) of oleamide was detected in human MGS. In the negative-ion mode, three major compounds with m/z values of 729, 757, and 785 that were apparently related to anionogenic lipids of the diacylglyceryl family were found in all of the samples. Common phospholipids and ceramides (Cers) were not present among the major MGS lipids. Phosphocholine-based lipids were found in MGS in quantities less than 0.01% (w/w), if at all. This ratio is two orders of magnitude lower than reported previously. These observations suggest that MGS are a major source of nonpolar lipids of the WE and Chl-E families for the tear film lipid layer, but not of its previously reported (phospho)lipid, Cer, and fatty acid amide components.

Possible involvement of gap junctions in the barrier function of tight junctions of brain and lung endothelial cells

Gap-junction plaques are often observed with tight-junction strands of vascular endothelial cells but the molecular interaction and functional relationships between these two junctions remain obscure. We herein show that gap-junction proteins connexin40 (Cx40) and Cx43 are colocalized and coprecipitated with tight-junction molecules occludin, claudin-5, and ZO-1 in porcine blood-brain barrier (BBB) endothelial cells. Gap junction blockers 18beta-glycyrrhetinic acid (18beta-GA) and oleamide (OA) did not influence expression of Cx40, Cx43, occludin, claudin-5, junctional adhesion molecule (JAM)-A, JAM-B, JAM-C, or ZO-1, or their subcellular localization in the porcine BBB endothelial cells. In contrast, these gap-junction blocking agents inhibited the barrier function of tight junctions in cells, determined by measurement of transendothelial electrical resistance and paracellular flux of mannitol and inulin. 18beta-GA also significantly reduced the barrier property in rat lung endothelial (RLE) cells expressing doxycycline-induced claudin-1, but did not change the interaction between Cx43 and either claudin-1 or ZO-1, nor their expression levels or subcellular distribution. These findings suggest that Cx40- and/or Cx43-based gap junctions might be required to maintain the endothelial barrier function without altering the expression and localization of the tight-junction components analyzed.

Brain uptake of radiolabeled N‐oleoyl‐dopamine in the rat

AbstractN‐acyl‐dopamines are a novel class of biologically active lipids that have recently been identified in the brain and have the potential to interact with neural signaling pathways. This study seeks to determine the ability of N‐oleoyl‐dopamine, a synthetic amide of oleic acid and dopamine, to cross the blood brain barrier. We determined the tissue content of radioactivity in selected brain regions, in a short‐run study design, following injections of [3H]N‐oleoyl‐dopamine (0.4 µCi) into the internal carotid artery in the rat. These results were compared with intracarotid injections of [3H]dopamine and with intravenous injections of both radiolabeled compounds. The level of radioactivity was determined using liquid scintillation and was expressed as the percentage of its total dose injected per gram of tissue. We found that the 15‐min brain uptake of radioactivity, with no distinct regional variations, amounted to about 6% following the intracarotid [3H]N‐oleoyl‐dopamine, which was a significant 3–4‐fold increase over that following similar administration of [3H]dopamine. Intravenous injections of [3H]N‐oleoyl‐dopamine gave a much smaller yield of radioactivity in brain tissue samples which was still severalfold greater than that for intravenous [3H]dopamine. Qualitative thin‐layered chromatography screening showed the presence of unchanged N‐oleoyl‐dopamine in the brain following injections. We conclude that N‐oleoyl‐dopamine has an appreciable ability to cross the blood‐brain barrier, which contrasts the limited transfer of dopamine alone. N‐oleoyl‐dopamine might exert physiological effects due to its known affinity for the central vanilloid receptors or to better satisfying the brain tissue demand for dopamine. The study suggests a potential pharmacological role for N‐oleoyl‐dopamine delivered exogenously in helping regulate the brain function. Drug Dev. Res. 60:217–224, 2003. © 2003 Wiley‐Liss, Inc.

Cannabinoid receptor-inactive N -acylethanolamines and other fatty acid amides: metabolism and function

Although it is now generally accepted that long-chain N -acylethanolamines and their precursors, N -acylethanolamine phospholipids, exist as trace constituents in virtually all vertebrate cells and tissues, their possible biological functions are just emerging. While anandamide (N -arachidonoylethanolamine) has received much attention due to its ability to bind to and activate cannabinoid receptors, the saturated and monounsaturated N -acylethanolamines, which usually represent the vast majority, are cannabinoid receptor-inactive but appear to interact with endocannabinoids and to have other signaling functions as well. Also, primary fatty acid amides, including the amide of oleic acid, which acts as a sleep-inducing agent, do not interact with cannabinoid receptors but are catabolically related to endocannabinoids. Here we review published information on the occurrence, metabolism, and possible signaling functions of the cannabinoid receptor-inactive N -acylethanolamines and primary fatty acid amides.

Deletion of the GABA(A) receptor beta 3 subunit eliminates the hypnotic actions of oleamide in mice.

Oleamide (OA) is an endogenous unsaturated fatty acid amide with demonstrated sleep promoting effects in rodents. The sleep enhancing actions of OA may be mediated through interactions with the GABAergic, serotonergic or cannabinergic receptor systems. In this study, we investigated the possible interaction of OA with the GABA(A )receptor by administering OA to mice with a targeted mutation of the GABAA receptor beta 3 subunit (Gabarb3-/-). Peripherally administered OA significantly decreased sleep latency and wake time, while it increased non-rapid eye movement and total sleep times in wild-type (Gabarb3+/+) mice. OA failed to have any sleep-wake effect in Gabarb3-/- mice. On 24 h baseline recordings, no differences between Gabarb3-/- and Gabarb3+/+ mice were observed, indicating that the lack of a pharmacological response to OA in the Gabarb3-/- animals was not secondary to disruptions in physiological. sleep. Therefore, one mechanism by which OA exerts its sleep effects may be through interactions with GABA(A) receptors containing the beta 3 subunit.

The hypnotic actions of oleamide are blocked by a cannabinoid receptor antagonist.

The unsaturated fatty acid amide oleamide (OA), which accumulates in the CSF of rats during sleep deprivation, induces electroencephalographically measured sleep when administered intracerebroventricularly. The mechanism of sleep induction by OA is unclear but may derive from enhancements of GABA or 5-HT receptor function, or alternatively from changes in the catabolism or uptake of the related fatty acid amide anandamide, an endogenous cannabinoid-1 (CB1) receptor ligand. The present study tests the latter hypothesis by administering OA alone and in combination with the CB1 receptor antagonist SR141716. As previously reported, 2.8 microg OA administered intracerebroventricularly significantly shortened electroencephalographic sleep latency. SR141716 in a dose of 3 microg had no effects on sleep by itself, but when co-administered with OA prevented its sleep-inducing effects. These data suggest that at least one aspect of the hypnotic action of OA involves interactions with the CB1 receptor system, possibly by blocking the metabolism of the endogenous CB1 receptor agonist anandamide.