Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
The human body contains endogenous cannabinoids (endocannabinoids) that elicit effects similar to those of Δ-tetrahydrocanabinol, the principal bioactive component of cannabis. The endocannabinoid virodhamine (O-AEA) is the constitutional isomer of the well-characterized cardioprotective and anti-inflammatory endocannabinoid anandamide (AEA). The chemical structures of O-AEA and AEA contain arachidonic acid (AA) and ethanolamine; however, AA in O-AEA is connected to ethanolamine via an ester linkage, whereas AA in AEA is connected through an amide linkage. O-AEA is involved in regulating blood pressure and cardiovascular function. We show that O-AEA is found at levels 9.6-fold higher than that of AEA in porcine left ventricle. On a separate note, the cytochrome P450 (CYP) epoxygenase CYP2J2 is the most abundant CYP in the heart where it catalyzes the metabolism of AA and AA-derived eCBs to bioactive epoxides that are involved in diverse cardiovascular functions. Herein, using competitive binding studies, kinetic metabolism measurements, molecular dynamics, and wound healing assays, we have shown that O-AEA is an endogenous inhibitor of CYP2J2 epoxygenase. As a result, the role of O-AEA as an endogenous eCB inhibitor of CYP2J2 may provide a new mode of regulation to control the activity of cardiovascular CYP2J2 in vivo and suggests a potential cross-talk between the cardiovascular endocannabinoids and the cytochrome P450 system.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262108 | PMC |
| http://dx.doi.org/10.1021/acs.biochem.8b00691 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Endocannabinoids as potential biomarkers: It's all about pre-analytics.
J Mass Spectrom Adv Clin Lab
November 2021
Institute of Clinical Pharmacology, pharmazentrum frankfurt/ZAFES, University Hospital of Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
Introduction: Arachidonoyl ethanolamide (AEA) and 2-arachidonoyl glycerol (2-AG) are central lipid mediators of the endocannabinoid system. They are highly relevant due to their involvement in a wide variety of inflammatory, metabolic or malign diseases. Further elucidation of their modes of action and use as biomarkers in an easily accessible matrix, like blood, is restricted by their susceptibility to deviations during blood sampling and physiological co-dependences, which results in high variability of reported concentrations in low ng/mL ranges.
View Article and Find Full Text PDFA simple LC-MS/MS method for the simultaneous quantification of endocannabinoids in biological samples.
J Chromatogr B Analyt Technol Biomed Life Sci
December 2020
Institute of Pharmacology and Toxicology, Rostock University Medical Center, Rostock, Germany. Electronic address:
The arachidonic acid derivatives N-arachidonoylethanolamine (anandamide; AEA), 2-arachidonoylglycerol (2-AG), N-arachidonoyldopamine (NADA), 2-arachidonoylglycerol ether (noladin ether; 2-AGE) and O-arachidonoylethanolamine (virodhamine; VA) were identified as physiological components of the endocannabinoid (EC) system. In order to gain further profound knowledge about the different EC-induced physiological and pathophysiological effects, appropriate analytical methods are required. The method described here uses liquid chromatography in combination with positive electrospray ionization mass spectrometry (LC-MS/MS) to quantify the concentrations of the above-mentioned EC compounds in cells.
View Article and Find Full Text PDFVirodhamine, an endocannabinoid, induces megakaryocyte differentiation by regulating MAPK activity and function of mitochondria.
J Cell Physiol
February 2021
Department of Biochemistry, University of Hyderabad, Hyderabad, Telangana, India.
Endocannabinoids are well-known regulators of neurotransmission by activating the cannabinoid (CB) receptors. Endocannabinoids are being used extensively for the treatment of various neurological disorders such as Alzheimer's and Parkinson's diseases. Although endocannabinoids are well studied in cell survival, proliferation, and differentiation in various neurological disorders and several cancers, the functional role in the regulation of blood cell development is less examined.
View Article and Find Full Text PDFDetermination of endocannabinoids and endocannabinoid-like substances in human K3EDTA plasma - LC-MS/MS method validation and pre-analytical characteristics.
Talanta
November 2019
Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University, Theodor-Stern-Kai 7, 60590, Frankfurt Am Main, Germany.
The determination of endocannabinoids and endocannabinoid-like substances in biological human samples is a vibrant field of research with great significance due to postulated relevance of these substances in diseases such as Alzheimer's disease, multiple sclerosis, cancer and cardiovascular diseases. For a possible use as biomarker in early prediction or diagnosis of a disease as well as examination of a successful treatment, the valid determination of the analytes in common accessible human samples, such as plasma or serum, is of great importance. A method for the determination of arachidonoyl ethanolamide, oleoyl ethanolamide, palmitoyl ethanolamide, 1-arachidonoyl glycerol and 2-arachidonoyl glycerol in human K3EDTA plasma using liquid-liquid-extraction in combination with liquid chromatography-tandem-mass spectrometry has been developed and validated for the quantification of the aforementioned analytes.
View Article and Find Full Text PDFEndocannabinoids and endocannabinoid-like compounds modulate hypoxia-induced permeability in CaCo-2 cells via CB, TRPV1, and PPARα.
Biochem Pharmacol
October 2019
Division of Medical Sciences & Graduate Entry Medicine, School of Medicine, Royal Derby Hospital, University of Nottingham, Nottingham, UK. Electronic address:
Background And Purpose: We have previously reported that endocannabinoids modulate permeability in Caco-2 cells under inflammatory conditions and hypothesised in the present study that endocannabinoids could also modulate permeability in ischemia/reperfusion.
Experimental Approach: Caco-2 cells were grown on cell culture inserts to confluence. Trans-epithelial electrical resistance (TEER) was used to measure permeability.