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Luca Navarini, Tiziana Bisogno, Pamela Mozetic, Fabiana Piscitelli, Domenico Paolo Emanuele Margiotta, Fabio Basta, Antonella Afeltra, Mauro Maccarrone
The endocannabinoid (eCB) system plays a key role in many physiological and pathological conditions and its dysregulation has been described in several rheumatological and autoimmune diseases. Yet, its possible alteration in systemic lupus erythematosus (SLE) has never been investigated. Here, we aimed filling this gap in plasma and peripheral blood mononuclear cells (PBMCs) of patients with SLE and age- and sex- matched healthy subjects (HS). Liquid chromatography-mass spectrometry quantitation of eCB levels highlighted that plasma levels of 2-arachidonoylglycerol (2-AG) were significantly increased in SLE patients compared to HS (p = 0...
April 12, 2018: International Journal of Biochemistry & Cell Biology
Giovanna Trinchese, Gina Cavaliere, Chiara De Filippo, Serena Aceto, Marina Prisco, Jong Tai Chun, Eduardo Penna, Rossella Negri, Laura Muredda, Andrea Demurtas, Sebastiano Banni, Roberto Berni-Canani, Giuseppina Mattace Raso, Antonio Calignano, Rosaria Meli, Luigi Greco, Marianna Crispino, Maria P Mollica
Scope: Milk from various species differs in nutrient composition. In particular, human milk (HM) and donkey milk (DM) are characterized by a relative high level of triacylglycerol enriched in palmitic acid in sn-2 position. These dietary fats seem to exert beneficial nutritional properties through N-acylethanolamine tissue modulation. The aim of this study is to compare the effects of cow milk (CM), DM, and HM on inflammation and glucose and lipid metabolism, focusing on mitochondrial function, efficiency, and dynamics in skeletal muscle, which is the major determinant of resting metabolic rate...
2018: Frontiers in Physiology
Rico Schwarz, Robert Ramer, Burkhard Hinz
The endocannabinoid system is currently under intense investigation due to the therapeutic potential of cannabinoid-based drugs as treatment options for a broad variety of diseases including cancer. Besides the canonical endocannabinoid system that includes the cannabinoid receptors CB1 and CB2 and the endocannabinoids N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol, recent investigations suggest that other fatty acid derivatives, receptors, enzymes, and lipid transporters likewise orchestrate this system as components of the endocannabinoid system when defined as an extended signaling network...
February 2018: Drug Metabolism Reviews
Raffaele Pezzilli, Pierangela Ciuffreda, Roberta Ottria, Alessandro Ravelli, Gianvico Melzi d'Eril, Alessandra Barassi
BACKGROUND: The endocannabinoid system plays a substantial role in analgesia. AIM: To analyze N-arachidonoylethanolamine (AEA), N-oleoylethanolamine (OEA), linoleoyl ethanolamide (LEA), α-linoleoyl ethanolamine (α-LNEA), N-palmitoylethanolamine (PEA) and N-stearoyl ethanolamine (SEA) in two groups of patients having chronic pancreatic diseases. PATIENTS AND METHODS: Twenty-six patients with chronic pancreatitis, 26 patients with pancreatic ductal adenocarcinoma and 36 healthy subjects were studied...
June 20, 2017: Scandinavian Journal of Gastroenterology
Jay S Kirkwood, Corey D Broeckling, Seth Donahue, Jessica E Prenni
Endocannabinoids (ECs) represent a class of endogenous, small molecules that bind and activate the G-protein coupled EC receptors. They are involved in a variety of fundamental biological processes and are associated with many disease states. Endocannabinoids are often present in complex matrices and at low concentrations, complicating their measurement. Here we describe a highly sensitive method for the quantitation of the following ECs in serum: N-arachidonoylethanolamine (anandamide), N-oleoylethanolamine, N-palmitoylethanolamine, 2-arachidonoylglycerol, and its inactive isomer 1-arachidonoylglycerol...
October 15, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Youngnam Kang, Hajime Sato, Mitsuru Saito, Dong Xu Yin, Sook Kyung Park, Seog Bae Oh, Yong Chul Bae, Hiroki Toyoda
Anandamide (AEA) and N-oleoylethanolamine (OEA) are produced in the intestine and brain during fasting and satiety, respectively. Subsequently, AEA facilitates food intake via activation of cannabinoid type-1 receptors (CB1Rs) while OEA decreases food intake via activation of peroxisome proliferator-activated receptor-α (PPARα) and/or G-protein-coupled receptor 119 (GPR119). Neuronal activity in the gastrointestinal region of the autonomic insula (GI-Au-I) that rostrally adjoins the gustatory insula (Gu-I) increases during fasting, enhancing appetite while umami and sweet taste sensations in Gu-I enhances appetite in GI-Au-I, strongly suggesting the presence of a neural interaction between the Gu-I and GI-Au-I which changes depending on the concentrations of AEA and OEA...
2016: Scientific Reports
Xudong Xu, Han Guo, Zuo Jing, Lichao Yang, Caixia Chen, Lu Peng, Xiaoqing Wang, Lu Yan, Rongting Ye, Xin Jin, Yiqing Wang
Inflammation plays a pivotal role in the pathogenesis of atherosclerosis. Peroxisome proliferator-activated receptor-alpha (PPAR-α) and cannabinoid receptor 2 (CB2) crucially impact the modulation of inflammation. N-Oleoylethanolamine (OEA), a natural agonist of PPAR-α, can also up-regulate the expression of CB2 in human umbilical vein endothelial cells (HUVECs) and further shows an antiatherosclerotic effect. Our study was designed to determinate whether OEA could inhibit inflammation in HUVECs induced by tumor necrosis factor-α (TNF-α) and to identify the mechanism of OEA function...
October 2016: Journal of Cardiovascular Pharmacology
T Venkatesan, Y Zadvornova, H Raff, C J Hillard
BACKGROUND: The endocannabinoid system and the hypothalamic-pituitary-adrenal axis are important neuromodulators of nausea and vomiting. This led us to hypothesize that patients with cyclic vomiting syndrome (CVS) have lower serum endocannabinoids (eCBs) and higher salivary cortisol and alpha amylase. METHODS: Serum eCBs and related lipids, N-oleoylethanolamine (OEA) and N-palmitoylethanolamide (PEA), and salivary cortisol, and alpha amylase (index of sympathetic nervous system activity) were measured in 22 CVS patients (age 40 ± 11, female = 17) in the well and sick phases and 12 matched controls (age 37 ± 12, female = 10)...
September 2016: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Katrin Winkler, Robert Ramer, Sophie Dithmer, Igor Ivanov, Jutta Merkord, Burkhard Hinz
Inhibition of endocannabinoid degradation has been suggested as tool for activation of endogenous tumor defense. One of these strategies lies in blockade of fatty acid amide hydrolase (FAAH) which catalyzes the degradation of endocannabinoids (anandamide [AEA], 2-arachidonoylglycerol [2-AG]) and endocannabinoid-like substances (N-oleoylethanolamine [OEA], N-palmitoylethanolamine [PEA]). This study addressed the impact of two FAAH inhibitors (arachidonoyl serotonin [AA-5HT], URB597) on A549 lung cancer cell metastasis and invasion...
March 22, 2016: Oncotarget
Ana Maria Sanchez, Raffaella Cioffi, Paola Viganò, Massimo Candiani, Roberta Verde, Fabiana Piscitelli, Vincenzo Di Marzo, Elisabetta Garavaglia, Paola Panina-Bordignon
Cannabinoids and modulators of the endocannabinoid system affect specific mechanisms that are critical to the establishment and development of endometriosis. The aim of this study was to measure the systemic levels of endocannabinoids and related mediators in women with and without endometriosis and to investigate whether such levels correlated with endometriosis-associated pain. Plasma and endometrial biopsies were obtained from women with a laparoscopic diagnosis of endometriosis (n = 27) and no endometrial pathology (n = 29)...
August 2016: Reproductive Sciences
Jantana Keereetaweep, Kent D Chapman
The endocannabinoids N-arachidonoylethanolamide (or anandamide, AEA) and 2-arachidonoylglycerol (2-AG) belong to the larger groups of N-acylethanolamines (NAEs) and monoacylglycerol (MAG) lipid classes, respectively. They are biologically active lipid molecules that activate G-protein-coupled cannabinoid receptors found in various organisms. After AEA and 2-AG were discovered in the 1990s, they have been extensively documented to have a broad range of physiological functions. Along with AEA, several NAEs, for example, N-palmitoylethanolamine (PEA), N-stearoylethanolamine (SEA), and N-oleoylethanolamine (OEA) are also present in tissues, usually at much larger concentrations than AEA...
2016: Neural Plasticity
Erin M Rock, Cheryl L Limebeer, Jordan M Ward, Arianne Cohen, Katherine Grove, Micah J Niphakis, Benjamin F Cravatt, Linda A Parker
RATIONALE: Fatty acid amide hydrolase (FAAH) inhibition elevates anandamide (AEA), which acts on cannabinoid (CB1 and CB2) receptors, as well as N-palmitoylethanolamide (PEA) and N-oleoylethanolamine (OEA), which act on peroxisome proliferator-activated receptor alpha (PPARα). Here, we determine the mechanism of action of FAAH inhibition on acute and anticipatory nausea (AN). OBJECTIVE: We compared the effectiveness and mechanism of action of two FAAH inhibitors, URB597 and PF-3845, to reduce acute nausea and AN in rodent models of conditioned gaping...
October 2015: Psychopharmacology
Yvonne Wollank, Robert Ramer, Igor Ivanov, Achim Salamon, Kirsten Peters, Burkhard Hinz
Regenerative activity in tissues of mesenchymal origin depends on the migratory potential of mesenchymal stem cells (MSCs). The present study focused on inhibitors of the enzyme fatty acid amide hydrolase (FAAH), which catalyzes the degradation of endocannabinoids (anandamide, 2-arachidonoylglycerol) and endocannabinoid-like substances (N-oleoylethanolamine, N-palmitoylethanolamine). Boyden chamber assays, the FAAH inhibitors, URB597 and arachidonoyl serotonin (AA-5HT), were found to increase the migration of human adipose-derived MSCs...
October 2015: Journal of Lipid Research
Caroline H Johnson, Gary J Patti, Jean-Philippe Courade, Leah P Shriver, Linh T Hoang, Marianne Manchester, Gary Siuzdak
Therapeutic options for neuropathic pain have improved over the last 20 years yet still only provide partial relief with numerous side effects. Recently, metabolomics revealed that the concentration of the endogenous metabolite N,N-dimethylsphingosine (DMS) is increased in the spinal cord in a model of neuropathic pain. Additionally, it was shown that introduction of DMS to the central nervous system (CNS) resulted in mechanical allodynia. Here, we have examined two compounds; pregabalin (Lyrica®), a drug used to treat neuropathic pain, and N-oleoylethanolamine (NOE), an endogenous endocannabinoid-like compound that is known to affect multiple lipid pathways...
September 2015: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
Jing Liu, Loren Parsons, Carey Pope
Parathion and chlorpyrifos are organophosphorus insecticides (OPs) that elicit acute toxicity by inhibiting acetylcholinesterase (AChE). The endocannabinoids (eCBs, N-arachidonoylethanolamine, AEA; 2-arachidonoylglycerol, 2AG) are endogenous neuromodulators that regulate presynaptic neurotransmitter release in neurons throughout the central and peripheral nervous systems. While substantial information is known about the eCBs, less is known about a number of endocannabinoid-like metabolites (eCBLs, e.g., N-palmitoylethanolamine, PEA; N-oleoylethanolamine, OEA)...
September 2015: Neurotoxicology
Yuan Gong, Xinmin Li, Lei Kang, Ying Xie, Zhengxing Rong, Hao Wang, Hong Qi, Hongzhuan Chen
The endocannabinoids (eCBs), N-arachidonoylethanolamine (anandamide, AEA) and 2-ararchidonylglycerol (2-AG) have been identified as main endogenous ligands for cannabinoid receptors. Developing a sensitive and robust method to determine AEA and 2-AG has been shown to be essential to understand their effects in stress regulation and the pathogenesis of affective disorders. Since eCBs are endogenous molecules, there is no true blank matrix available to construct calibration curves, thus, it has been a challenge to determine eCBs in plasma and brain matrix...
2015: Journal of Pharmaceutical and Biomedical Analysis
Igor Ivanov, Philipp Borchert, Burkhard Hinz
The endocannabinoid system has been considered as a target for pharmacological intervention. Accordingly, inhibition of fatty acid amide hydrolase (FAAH), a degrading enzyme of the endocannabinoids N-arachidonoylethanolamine (anandamide; AEA) and 2-arachidonoylglycerol (2-AG) as well as of the endocannabinoid-like substances N-oleoylethanolamine (OEA) and N-palmitoylethanolamine (PEA), can cause augmented endogenous cannabinoid tone. Using liquid chromatography coupled with positive electrospray ionisation mass spectrometry, we herein describe a method to simultaneously quantify levels of AEA, OEA, PEA and 2-AG in cultured cells...
February 2015: Analytical and Bioanalytical Chemistry
Minghuan Fu, Zhihong Li, Tao Tan, Weixin Guo, Nanzi Xie, Qing Liu, Hua Zhu, Xiaoyun Xie, Han Lei
Palmitate (PA) impairs endothelial progenitor cells (EPCs). However, the molecular mechanism underlying the suppressive function of PA remains largely unknown. Ceramide, a free fatty acid metabolite, mediates multiple cellular signals. We hypothesized that ceramide acts as an intermediate molecule to mediate inhibition of EPCs by PA. We first demonstrated that PA could inhibit the attachment, migration, and tube formation of EPCs through suppression of the Akt/endothelial nitric oxide (NO) synthase (eNOS) signaling pathway...
January 1, 2015: American Journal of Physiology. Heart and Circulatory Physiology
Rocio Bautista-Pérez, Leonardo del Valle-Mondragón, Agustina Cano-Martínez, Oscar Pérez-Méndez, Bruno Escalante, Martha Franco
The possibility that angiotensin II (ANG II) exerts its effects through the activation of neutral sphingomyelinase (nSMase) has not been tested in kidneys. The results of the present study provide evidence for the activity and expression of nSMase in rat kidneys. In isolated perfused rat kidney, ANG II-induced renal vasoconstriction was inhibited by GW4869, an inhibitor of nSMase. We used nSMase for investigating the signal transduction downstream of ceramide. nSMase constricted the renal vasculature. An inhibitor of ceramidase (CDase), N-oleoylethanolamine (OEA), enhanced either ANG II- or nSMase-induced renal vasoconstriction...
May 15, 2015: American Journal of Physiology. Renal Physiology
Ya-Ting Gai, Qiang Shu, Cai-Xia Chen, You-Lin Lai, Wen-Jun Li, Lu Peng, Li-Min Lin, Xin Jin
To observe a PPAR-alpha agonist effect of N-oleoylethanolamine (OEA) on CB2 (cannabinoid receptor 2), an anti-inflammatory receptor in vascular endothelial cell, healthy HUVECs and TNF-alpha induced HUVECs were used to establish a human vascular endothelial cell inflammatory model. Different doses of OEA (10, 50 and 100 micromol x L(-1)) had been given to HUVECs, cultured at 37 degrees C for 7 h and then collected the total protein and total mRNA. CB2 protein expression was detected by Western blotting and CB2 mRNA expression was assayed by real-time PCR...
March 2014: Yao Xue Xue Bao, Acta Pharmaceutica Sinica
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