virodhamine has been researched along with anandamide* in 13 studies
1 review(s) available for virodhamine and anandamide
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The endocannabinoid system: drug targets, lead compounds, and potential therapeutic applications.
Topics: Amides; Amidohydrolases; Amines; Animals; Arachidonic Acids; Binding Sites; Cannabinoid Receptor Modulators; Drug Design; Endocannabinoids; Esters; Ethers; Glycerides; Humans; Ligands; Monoacylglycerol Lipases; Polyunsaturated Alkamides; Receptors, Cannabinoid | 2005 |
12 other study(ies) available for virodhamine and anandamide
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Endocannabinoid Virodhamine Is an Endogenous Inhibitor of Human Cardiovascular CYP2J2 Epoxygenase.
The human body contains endogenous cannabinoids (endocannabinoids) that elicit effects similar to those of Δ Topics: Animals; Arachidonic Acids; Cannabinoid Receptor Modulators; Cannabinoids; Cytochrome P-450 CYP2J2; Cytochrome P-450 Enzyme System; Endocannabinoids; Heart; Human Umbilical Vein Endothelial Cells; Humans; Molecular Docking Simulation; Polyunsaturated Alkamides; Protein Conformation; Swine; Wound Healing | 2018 |
Mechanism of platelet activation induced by endocannabinoids in blood and plasma.
Platelets play a central role in atherosclerosis and atherothrombosis, and circulating endocannabinoids might modulate platelet function. Previous studies concerning effects of anandamide (N-arachidonylethanolamide) and 2-arachidonoylglycerol (2-AG) on platelets, mainly performed on isolated cells, provided conflicting results. We therefore investigated the action of three main endocannabinoids [anandamide, 2-AG and virodhamine (arachidonoylethanolamine)] on human platelets in blood and platelet-rich plasma (PRP). 2-AG and virodhamine induced platelet aggregation in blood, and shape change, aggregation and adenosine triphosphate (ATP) secretion in PRP. The EC50 of 2-AG and virodhamine for platelet aggregation in blood was 97 and 160 µM, respectively. Lower concentrations of 2-AG (20 µM) and virodhamine (50 µM) synergistically induced aggregation with other platelet stimuli. Platelet activation induced by 2-AG and virodhamine resembled arachidonic acid (AA)-induced aggregation: shape change, the first platelet response, ATP secretion and aggregation induced by 2-AG and virodhamine were all blocked by acetylsalicylic acid (ASA) or the specific thromboxane A2 (TXA2) antagonist daltroban. In addition, platelet activation induced by 2-AG and virodhamine in blood and PRP were inhibited by JZL184, a selective inhibitor of monoacylglycerol lipase (MAGL). In contrast to 2-AG and virodhamine, anandamide, a substrate of fatty acid amidohydrolase, was inactive. Synthetic cannabinoid receptor subtype 1 (CB1) and 2 (CB2) agonists lacked stimulatory as well as inhibitory platelet activity. We conclude that 2-AG and virodhamine stimulate platelets in blood and PRP by a MAGL-triggered mechanism leading to free AA and its metabolism by platelet cyclooxygenase-1/thromboxane synthase to TXA2. CB1, CB2 or non-CB1/CB2 receptors are not involved. Our results imply that ASA and MAGL inhibitors will protect platelets from activation by high endocannabinoid levels, and that pharmacological CB1- and CB2-receptor ligands will not affect platelets and platelet-dependent progression and complications of cardiovascular diseases. Topics: Adult; Arachidonic Acids; Blood Platelets; Cannabinoids; Cyclooxygenase 1; Endocannabinoids; Glycerides; Humans; Platelet Activation; Platelet Aggregation Inhibitors; Polyunsaturated Alkamides | 2014 |
The effects of cannabidiol on the antigen-induced contraction of airways smooth muscle in the guinea-pig.
(-)-Δ(9)-Tetrahydrocannabinol has been demonstrated to have beneficial effects in the airways, but its psychoactive effects preclude its therapeutic use for the treatment of airways diseases. In the present study we have investigated the effects of (-)-cannabidiol, a non-psychoactive component of cannabis for its actions on bronchial smooth muscle in vitro and in vivo. Guinea-pig bronchial smooth muscle contractions induced by exogenously applied spasmogens were measured isometrically. In addition, contractile responses of bronchial smooth muscle from ovalbumin-sensitized guinea-pigs were investigated in the absence or presence of (-)-cannabidiol. Furthermore, the effect of (-)-cannabidiol against ovalbumin-induced airway obstruction was investigated in vivo in ovalbumin-sensitized guinea-pigs. (-)-Cannabidiol did not influence the bronchial smooth muscle contraction induced by carbachol, histamine or neurokinin A. In contrast, (-)-cannabidiol inhibited anandamide- and virodhamine-induced responses of isolated bronchi. A fatty acid amide hydrolase inhibitor, phenylmethanesulfonyl fluoride reversed the inhibitory effect of (-)-cannabidiol on anandamide-induced contractions. In addition, (-)-cannabidiol inhibited the contractile response of bronchi obtained from allergic guinea-pigs induced by ovalbumin. In vivo, (-)-cannabidiol reduced ovalbumin-induced airway obstruction. In conclusion, our results suggest that cannabidiol can influence antigen-induced airway smooth muscle tone suggesting that this molecule may have beneficial effects in the treatment of obstructive airway disorders. Topics: Airway Obstruction; Animals; Arachidonic Acids; Bronchi; Cannabidiol; Cannabinoids; Carbachol; Endocannabinoids; Female; Guinea Pigs; Histamine; In Vitro Techniques; Male; Muscle Contraction; Muscle, Smooth; Neurokinin A; Ovalbumin; Phenylmethylsulfonyl Fluoride; Polyunsaturated Alkamides | 2013 |
The endocannabinoids anandamide and virodhamine modulate the activity of the candidate cannabinoid receptor GPR55.
The role of cannabinoid receptors in inflammation has been the topic of many research endeavors. Despite this effort, to date the involvement of the endocannabinoid system (ECS) in inflammation remains obscure. The ambiguity of cannabinoid involvement may be explained by the existence of cannabinoid receptors, other than CB(1) and CB(2), or a consequence of interaction of endocannabinoids with other signaling systems. GPR55 has been proposed to be a cannabinoid receptor; however the interaction of the endocannabinoid system with GPR55 remains elusive. Consequently this study set about to examine the effects of the endocannabinoids, anandamide (AEA) and virodhamine, on GPR55 mediated signaling. Specifically, we assessed changes in β-arrestin2 (βarr2) distribution and GPR55 receptor internalization following activation by lysophosphatidylinositol (LPI), the synthetic cannabinoid ligand SR141716A, and new selective synthetic GPR55 agonists. Data obtained from the experiments presented herein demonstrate that AEA and virodhamine modulate agonist-mediated recruitment of βarr2. AEA and virodhamine act as partial agonists; enhancing the agonist effect at low concentrations and inhibiting it at high concentrations. Furthermore, both virodhamine and AEA significantly attenuated agonist-induced internalization of GPR55. These effects are attributed to the expression of GPR55, and not CB(1) and CB(2) receptors, as we have established negligible expression of CB(1) and CB(2) in these GPR55-transfected U2OS cells. The identification of select endocannabinoids as GPR55 modulators will aide in elucidating the function of GPR55 in the ECS. Topics: Animals; Arachidonic Acids; Arrestins; beta-Arrestins; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Cannabinoids; Cell Line; Cell Survival; CHO Cells; Cricetinae; Cricetulus; Endocannabinoids; Green Fluorescent Proteins; HEK293 Cells; Humans; Immunohistochemistry; L-Lactate Dehydrogenase; Microscopy, Confocal; Polyunsaturated Alkamides; Real-Time Polymerase Chain Reaction; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Receptors, Cannabinoid; Receptors, G-Protein-Coupled; RNA | 2012 |
The molecular basis for neuroimmune receptor signaling.
Many of the receptors which are responsible for the responses to the common drugs of abuse belong to the G protein-coupled receptor (GPCR) family. In this special issue of the Journal of Neuroimmune Pharmacology a collection of papers is presented which deals with signaling events that are important for the function of these receptors. Because these receptors are expressed by both neuronal and immune cells, and because these receptors play a complex role in regulating function in both the nervous and immune systems, a more complete understanding of the regulation of expression of these receptors is essential. Moreover, once these receptors are expressed and activated, a complex series of signaling events are initiated that can have substantial significance. We have only a limited understanding of these signaling events, but with more complete information, we may be able to control the undesirable and/or desirable consequences of receptor activation by drugs of abuse. Topics: Analgesics, Opioid; Animals; Arachidonic Acids; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Cannabinoids; Chemokine CXCL12; Dronabinol; Endocannabinoids; Female; HIV Envelope Protein gp120; HIV-1; Humans; Lymphocyte Activation; Lymphocytes; MicroRNAs; Morphine; Narcotics; Neostriatum; Nervous System; Neurons; Polyunsaturated Alkamides; Pregnancy; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Receptors, Cannabinoid; Receptors, G-Protein-Coupled; Receptors, Opioid, mu; Signal Transduction; T-Lymphocytes; T-Lymphocytes, Cytotoxic | 2012 |
Simultaneous quantitative analysis of N-acylethanolamides in clinical samples.
A simple and rapid analytical method is described for the simultaneous quantitative analysis of three different N-acylethanolamides in human biological samples: anandamide (AEA), oleoylethanolamide (OEA), and palmitoylethanolamide (PEA). The method is based on a new hybrid solid phase extraction-precipitation technology followed by ultra-performance liquid chromatography/mass spectrometry (UPLC/MS) analysis using d(4)-AEA as the internal standard. The method is linear up to 100ng/ml with a limit of quantitation of 50pg/ml for AEA and 100pg/ml for OEA and PEA. Good reproducibility, accuracy, and precision were demonstrated during the method validation. Application of this new methodology to the analysis of clinical study samples is presented. Topics: Adolescent; Adult; Amides; Amidohydrolases; Arachidonic Acids; Calibration; Cannabinoids; Chromatography, High Pressure Liquid; Endocannabinoids; Enzyme Inhibitors; Ethanolamines; Female; Humans; Leukocytes, Mononuclear; Male; Middle Aged; Molecular Structure; Oleic Acids; Palmitic Acids; Polyunsaturated Alkamides; Reproducibility of Results; Semen; Solid Phase Microextraction; Tandem Mass Spectrometry; Young Adult | 2009 |
Ultra performance liquid chromatography tandem mass spectrometry method for the measurement of anandamide in human plasma.
Anandamide (N-arachidonoylethanolamine, AEA) is an endocannabinoid present in human plasma that is associated with several physiological functions and disease states. Significant variability in AEA plasma concentrations has been reported between studies, because quantification of AEA is fraught with methodological difficulties. A rapid, highly sensitive, robust, specific, and highly reproducible ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method is described here for the analysis of AEA in human plasma. This fully validated method using octa-deuterated AEA (AEA-d8) as an internal standard represents an improvement over previous analyses in terms of run time (4 min), limit of detection (0.055 fmol on column, 18.75 fmol/ml plasma), precision (relative standard deviations of 3.7, 3.9, and 4.8% for 1.66, 6.65, and 133 fmol on column), and accuracy (97.5-104.5%). AEA analysis was linear over the range 0.23 to 19 nM (1.66 to 133 fmol on column). To demonstrate the usefulness of this method for the measurement of AEA levels in clinical samples, plasma samples obtained from female volunteers at different stages of the menstrual cycle and pregnant women were assayed. Plasma AEA concentrations were significantly (P=0.0078) lower in the luteal phase of the menstrual cycle compared to the follicular phase. In pregnancy, the concentrations were lowest in the first and second trimesters with levels comparable to those observed in the luteal phase of the menstrual cycle and modestly increased in the third trimester. The highest plasma AEA levels were observed in women in active labour, and these were significantly (P=0.0147) higher than those observed in women at term but not in active labour. Postmenopausal women had AEA concentrations comparable to levels observed during the luteal phase of premenopausal women and were significantly (P=0.0389) lower than AEA plasma concentrations obtained during the follicular phase. The sensitivity and precision of the validated method described here suggests that this method is suitable for the analysis of AEA in clinical samples and may be utilised for the investigation of biomatrices containing limited amounts of AEA. Topics: Age Factors; Arachidonic Acids; Cannabinoids; Chromatography, High Pressure Liquid; Endocannabinoids; Female; Humans; Menstrual Cycle; Polyunsaturated Alkamides; Postmenopause; Pregnancy; Reproducibility of Results; Tandem Mass Spectrometry | 2008 |
The orphan receptor GPR55 is a novel cannabinoid receptor.
The endocannabinoid system functions through two well characterized receptor systems, the CB1 and CB2 receptors. Work by a number of groups in recent years has provided evidence that the system is more complicated and additional receptor types should exist to explain ligand activity in a number of physiological processes.. Cells transfected with the human cDNA for GPR55 were tested for their ability to bind and to mediate GTPgammaS binding by cannabinoid ligands. Using an antibody and peptide blocking approach, the nature of the G-protein coupling was determined and further demonstrated by measuring activity of downstream signalling pathways.. We demonstrate that GPR55 binds to and is activated by the cannabinoid ligand CP55940. In addition endocannabinoids including anandamide and virodhamine activate GTPgammaS binding via GPR55 with nM potencies. Ligands such as cannabidiol and abnormal cannabidiol which exhibit no CB1 or CB2 activity and are believed to function at a novel cannabinoid receptor, also showed activity at GPR55. GPR55 couples to Galpha13 and can mediate activation of rhoA, cdc42 and rac1.. These data suggest that GPR55 is a novel cannabinoid receptor, and its ligand profile with respect to CB1 and CB2 described here will permit delineation of its physiological function(s). Topics: Amino Acid Sequence; Animals; Arachidonic Acids; Binding Sites; Binding, Competitive; Cannabidiol; Cannabinoids; Cell Line; Cloning, Molecular; Cyclohexanols; Down-Regulation; Endocannabinoids; Guanosine 5'-O-(3-Thiotriphosphate); Humans; Ligands; Mice; Molecular Sequence Data; Organ Specificity; Polymerase Chain Reaction; Polyunsaturated Alkamides; Rats; Receptors, Cannabinoid; Receptors, G-Protein-Coupled; RNA, Messenger; Signal Transduction; Structure-Activity Relationship | 2007 |
Quantitative profiling of endocannabinoids and related compounds in rat brain using liquid chromatography-tandem electrospray ionization mass spectrometry.
A sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method is described for the simultaneous identification and quantification of eight endocannabinoid (EC) or related "entourage" compounds in rat brain tissue. Analytes were extracted and purified from rat brain tissue using an ethyl acetate/hexane solvent extraction, followed by a solid phase extraction (SPE) protocol. Chromatographic separation was achieved using a gradient elution, with a mobile phase of acetonitrile, formic acid, and ammonium acetate, at pH 3.6. A Thermo Hypersil C8 HyPurity Advance column (100x2.1 mm i.d., 3 microm) was used with a flow rate of 0.3 ml/min). Anandamide (AEA), 2-arachidonyl glycerol (2-AG), 2-arachidonylglyceryl ether (noladin ether), O-arachidonyl ethanolamide (virodhamine), 2-linoleoyl glycerol (2-LG), arachidonyl glycine, oleoyl ethanolamide (OEA), and palmitoyl ethanolamide (PEA) were quantified by positive ion tandem electrospray ionization mass spectrometry. Internal standards were deuterated AEA, deuterated 2-AG, and heptadecanoyl ethanolamide (HEA). Linearity was proven over the range of 25 fmol to 250 pmol, with a limit of detection of 25 fmol on column for all analytes except 2-AG, noladin ether, and 2-LG (250 fmol). This corresponded to a limit of quantification in biological tissue of 10 pmol/g for all analytes except 2-AG (100 pmol/g). Intra- and interday precision in biological tissue was routinely approximately 20% or lower, and accuracy was between 65% and 155%. This method was used to quantitatively profile regional differences in nine discrete rat brain regions for AEA, 2-AG, 2-LG, OEA, PEA, noladin ether, virodhamine, and arachidonyl glycine. Topics: Animals; Arachidonic Acids; Brain Chemistry; Cannabinoid Receptor Modulators; Cannabinoids; Chromatography, Liquid; Endocannabinoids; Glycerides; Glycine; Male; Oleic Acids; Polyunsaturated Alkamides; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry | 2007 |
Cannabinoid activation of PPAR alpha; a novel neuroprotective mechanism.
Although CB(1) receptor activation evokes neuroprotection in response to cannabinoids, some cannabinoids have been reported to be peroxisome proliferator activated receptor (PPAR) ligands, offering an alternative protective mechanism. We have, therefore, investigated the ability of a range of cannabinoids to activate PPAR alpha and for N-oleoylethanolamine (OEA), an endogenous cannabinoid-like compound (ECL), to evoke neuroprotection.. Assays of PPAR alpha occupancy and gene transactivation potential were conducted in cell-free and transfected HeLa cell preparations, respectively. In vivo estimates of PPAR alpha activation through fat mobilization and gene transcription were conducted in mice. Neuroprotection in vivo was investigated in wild-type and PPAR alpha gene-disrupted mice.. The ECLs OEA, anandamide, noladin ether and virodhamine were found to bind to the purified PPAR alpha ligand binding domain and to increase PPAR alpha-driven transcriptional activity. The high affinity synthetic CB(1/2) cannabinoid agonist WIN 55212-2 bound to PPAR alpha equipotently with the PPARalpha agonist fenofibrate, and stimulated PPARalpha-mediated gene transcription. The phytocannabinoid delta 9 tetrahydrocannabinol was without effect. OEA and WIN 55212-2 induced lipolysis in vivo, while OEA pre-treatment reduced infarct volume from middle cerebral artery occlusion in wild-type, but not in PPAR alpha-null mice. OEA treatment also led to increased expression of the NFkappa B-inhibitory protein, Ikappa B, in mouse cerebral cortex, while expression of the NFkappa B-regulated protein COX-2 was inhibited.. These data demonstrate the potential for a range of cannabinoid compounds, of diverse structures, to activate PPAR alpha and suggest that at least some of the neuroprotective properties of these agents could be mediated by nuclear receptor activation. Topics: Animals; Arachidonic Acids; Benzoxazines; Cannabinoids; Cerebral Cortex; Cyclooxygenase 2; Dronabinol; Endocannabinoids; Fatty Acids, Unsaturated; Fenofibrate; HeLa Cells; Humans; I-kappa B Kinase; Ligands; Luciferases; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Morpholines; Naphthalenes; Neuroprotective Agents; Oleic Acids; Polyunsaturated Alkamides; PPAR alpha; Protein Binding; Recombinant Fusion Proteins; Transfection | 2007 |
Persistent anxiogenic effects of a single or repeated doses of cocaine and methamphetamine: interactions with endogenous cannabinoid receptor ligands.
As persistent behavioural changes, such as increased anxiety-related behaviours, can be predicted based on the phenomenon of psychostimulant-induced neuronal plasticity, the time course (3-, 5- and 10-day time points) of the effects of both a single and repeated (daily for 7 days) i.p. administrations of cocaine (COC) and methamphetamine (MA) on anxiety-related behavioural symptoms in the elevated plus-maze test were examined in mice. Furthermore, based on the reported interactions between brain dopamine versus cannabinoid (CB) receptors and the contribution of CB receptors to the occurrence of persistent anxiety-related behavioural symptoms, the interactions of the agonist CP 55940 (CP) and the endogenous ligands anandamide (arachidonylethanolamide: AEA), 2-arachidonylglycerol (ARA), N-arachidonyldopamine (NADA), noladin ether (NL), and virodhamine (VA) with the COC- or MA-induced anxiety-related behaviours were also studied. In both an acute experiment using a single COC (30 mg/kg) or MA (4 mg/kg) dose and a chronic experiment using repeated COC (15 mg/kg) or MA (2 mg/kg) doses, anxiety-related behavioural symptoms were observed similarly at 3- and 5-day time points, but disappeared at the 10-day time point. Among the CB ligands, the agonists CP, AEA, ARA, NADA, and NL provided strong protective effects against each parameter at 3- and 5-day time points. Therefore, it was concluded that both COC and MA caused persistent anxiety-related behavioural symptoms following both a single and repeated treatments. Since these anxiogenic effects were attenuated by the endogenous CB agonists, the involvement of brain CB receptors was suspected. Topics: Analysis of Variance; Animals; Anxiety; Arachidonic Acids; Behavior, Animal; Cannabinoids; Cocaine; Cyclohexanols; Dopamine; Dose-Response Relationship, Drug; Drug Interactions; Endocannabinoids; Glycerides; Injections, Intraperitoneal; Male; Maze Learning; Methamphetamine; Mice; Mice, Inbred ICR; Polyunsaturated Alkamides; Receptor, Cannabinoid, CB1; Time Factors | 2005 |
Characterization of a novel endocannabinoid, virodhamine, with antagonist activity at the CB1 receptor.
The first endocannabinoid, anandamide, was discovered in 1992. Since then, two other endocannabinoid agonists have been identified, 2-arachidonyl glycerol and, more recently, noladin ether. Here, we report the identification and pharmacological characterization of a novel endocannabinoid, virodhamine, with antagonist properties at the CB1 cannabinoid receptor. Virodhamine is arachidonic acid and ethanolamine joined by an ester linkage. Concentrations of virodhamine measured by liquid chromatography atmospheric pressure chemical ionization-tandem mass spectrometry in rat brain and human hippocampus were similar to anandamide. In peripheral tissues that express the CB2 cannabinoid receptor, virodhamine concentrations were 2- to 9-fold higher than anandamide. In contrast to previously described endocannabinoids, virodhamine was a partial agonist with in vivo antagonist activity at the CB1 receptor. However, at the CB2 receptor, virodhamine acted as a full agonist. Transport of [(14)C]anandamide by RBL-2H3 cells was inhibited by virodhamine. Virodhamine produced hypothermia in the mouse and acted as an antagonist in the presence of anandamide both in vivo and in vitro. As a potential endogenous antagonist at the CB1 receptor, virodhamine adds a new form of regulation to the endocannabinoid system. Topics: Animals; Arachidonic Acids; Body Temperature; Brain; Cannabinoid Receptor Modulators; Cannabinoids; Dose-Response Relationship, Drug; Endocannabinoids; Ethanolamine; Hippocampus; Male; Mice; Polyunsaturated Alkamides; Rats; Rats, Wistar; Receptor, Cannabinoid, CB2; Receptors, Cannabinoid; Receptors, Drug | 2002 |