Induction of cyclooxygenase-2 by anandamide in cerebral microvascular endothelium

Ping Chen, Shanming Hu, Jianrong Yao, Steven A. Moore, Arthur A. Spector, Xiang Fang

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

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 PGE2 production as AEA. The PGE2 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.

Original languageEnglish (US)
Pages (from-to)28-35
Number of pages8
JournalMicrovascular research
Volume69
Issue number1-2
DOIs
StatePublished - Jan 2005
Externally publishedYes

Keywords

  • Anandamide
  • Cannabinoid receptor
  • Cyclooxgenase-2
  • Endothelial cells

ASJC Scopus subject areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine
  • Cell Biology

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