Journal article
Induction of cyclooxygenase-2 by anandamide in cerebral microvascular endothelium
Microvascular research, Vol.69(1), pp.28-35
2005
DOI: 10.1016/j.mvr.2005.02.001
PMID: 15797258
Abstract
Anandamide (AEA), an endogenous cannabinoid receptor agonist, is a potent vasodilator in the cerebral microcirculation. AEA is converted to arachidonic acid (AA) by fatty acid amidohydrolase (FAAH), and the conversion of AA to prostaglandins has been proposed as a potential mechanism for the vasodilation. Although AEA stimulated prostaglandin production by mouse cerebral microvascular endothelial cells, no [
3H]prostaglandins were produced when these cells were incubated with [
3H]AEA. Incubation with
R(+)-methanandamide (MAEA), a stable analogue of AEA that is not a substrate for FAAH, produced a similar increase in PGE
2 production as AEA. The PGE
2 production induced by either AEA or MAEA was completely inhibited by NS-398, a selective cyclooxygenase (COX)-2 inhibitor, suggesting that COX-2 was induced. AEA and MAEA increased the expression of COX-2 protein in a time-dependent manner. This increase occurred as early as 1 h and reached maximum at 2 h. Induction of COX-2 protein by AEA was partially inhibited by AM-251, a selective cannabinoid receptor-1 antagonist. Furthermore, AEA increased COX-2 promoter activity approximately twofold above baseline in a fragment ranging from −1432 to +59, the full-length of the COX-2 promoter, and the increase in COX-2 promoter activity produced by AEA was partially inhibited by AM-251. These results indicate that AEA increased COX-2 expression at the transcriptional level through, at least in part, a cannabinoid receptor-1-mediated mechanism in cerebral microvascular endothelium.
Details
- Title: Subtitle
- Induction of cyclooxygenase-2 by anandamide in cerebral microvascular endothelium
- Creators
- Ping Chen - Department of Biochemistry, 4-403 BSB, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USAShanming Hu - Department of Biochemistry, 4-403 BSB, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USAJianrong Yao - Department of Biochemistry, 4-403 BSB, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USASteven A Moore - Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USAArthur A Spector - Department of Biochemistry, 4-403 BSB, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USAXiang Fang - Department of Biochemistry, 4-403 BSB, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Microvascular research, Vol.69(1), pp.28-35
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.mvr.2005.02.001
- PMID
- 15797258
- ISSN
- 0026-2862
- eISSN
- 1095-9319
- Language
- English
- Date published
- 2005
- Academic Unit
- Stead Family Department of Pediatrics; Pathology; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9984046901602771
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