Journal article
Metabolism of anandamide in cerebral microvascular endothelial cells
Prostaglandins & other lipid mediators, Vol.73(1), pp.59-72
2004
DOI: 10.1016/j.prostaglandins.2003.11.005
PMID: 15165032
Abstract
Anandamide (
N-arachidonoylethanolamine, AEA), an endogenous cannabinoid receptor agonist, causes potent vasodilation in the cerebral circulation through an endothelial-dependent or -independent mechanism. We have investigated the processing of [
3
H
]AEA in cultured mouse cerebral microvascular endothelial cells (MEC) in order to better understand its mechanism of action in the cerebral vasculature. These cells took up anandamide very quickly, reaching a maximum value in 5
min and remaining at that level for at least 8
h. Analysis of the cell lipids demonstrated that, in addition to free anandamide, radioactivity was incorporated into phosphatidylcholine (PC), phosphatidylinositol (PI), and phosphatidylethanolamine (PE) in a time-dependent manner. Analysis of the hydrolyzed cell lipids indicated that anandamide was converted to arachidonic acid, a process that was inhibited by the selective fatty acid amide hydrolase inhibitor oleyl trifluoromethyl ketone (OTMK). Phospholipase A
2 (PLA
2) hydrolysis of the PC, PI, and PE fractions indicated that the arachidonic acid formed from anandamide was esterified predominately into
sn-2 position of the endothelial phospholipids. Furthermore, anandamide and arachidonic acid were released when the cells were incubated with A23187. These results suggest that the biological activity of anandamide might be regulated by its rapid uptake and calcium-dependent release in endothelial cells, and conversion of anandamide to arachidonic acid might serve as an inactivation process in the cerebral microcirculation.
Details
- Title: Subtitle
- Metabolism of anandamide in cerebral microvascular endothelial cells
- Creators
- Ping Chen - Department of Biochemistry, University of Iowa College of Medicine, 4-403 BSB, Iowa City, IA 52242, USAShanming Hu - Department of Biochemistry, University of Iowa College of Medicine, 4-403 BSB, Iowa City, IA 52242, USAShawn D Harmon - Department of Biochemistry, University of Iowa College of Medicine, 4-403 BSB, Iowa City, IA 52242, USASteven A Moore - Department of Pathology, University of Iowa College of Medicine, Iowa City, IA 52242, USAArthur A Spector - Department of Biochemistry, University of Iowa College of Medicine, 4-403 BSB, Iowa City, IA 52242, USAXiang Fang - Department of Biochemistry, University of Iowa College of Medicine, 4-403 BSB, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Prostaglandins & other lipid mediators, Vol.73(1), pp.59-72
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.prostaglandins.2003.11.005
- PMID
- 15165032
- ISSN
- 1098-8823
- eISSN
- 2212-196X
- Language
- English
- Date published
- 2004
- Academic Unit
- Stead Family Department of Pediatrics; Pathology; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9984047684102771
Metrics
14 Record Views