Human brain capillary endothelium: 2-Arachidonoglycerol (endocannabinoid) interacts with endothelin-1

Ye Chen, Richard M. McCarron, Yukoh Ohara, Joliet Bembry, Nabil Azzam, Frederick Lenz, Esther Shohami, Raphael Mechoulam, Maria Spatz

Research output: Contribution to journalArticle

Abstract

In brain, the regulatory mechanism of the endothelial reactivity to nitric oxide and endothelin-1 may involve Ca2+, cytoskeleton, and vasodilator-stimulated phosphoprotein changes mediated by the cGMP/cGMP kinase system. Endothelium of human brain capillaries or microvessels is used to examine the interplay of endothelin-1 with the putative vasorelaxant 2-arachidonoyl glycerol, an endogenous cannabimimetic derivative of arachidonic acid. This study demonstrates that 2-arachidonoyl glycerol counteracts Ca2+ mobilization and cytoskeleton rearrangement induced by endothelin-1. This event is independent of nitric oxide, cyclooxygenase, and lipoxygenase and is mediated in part by cannabimimetic CB1 receptor, G protein, phosphoinositol signal transduction pathway, and Ca2+-activated K+ channels. The induced rearrangements of cellular cytoskeleton (actin or vimentin) are partly prevented by inhibition of protein kinase C or high levels of potassium chloride. The 2-arachidonoyl glycerol-induced phosphorylation of vasodilator-stimulated phosphoprotein is mediated by cAMP. These findings suggest that 2-arachidonoyl glycerol may contribute to the regulation of cerebral capillary and microvascular function.

Original languageEnglish (US)
Pages (from-to)323-327
Number of pages5
JournalCirculation Research
Volume87
Issue number4
Publication statusPublished - Aug 18 2000

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Keywords

  • 2-arachidonoglycerol
  • Brain endothelial function
  • Cannabinoids
  • Endothelin-1
  • Endothelium

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Chen, Y., McCarron, R. M., Ohara, Y., Bembry, J., Azzam, N., Lenz, F., ... Spatz, M. (2000). Human brain capillary endothelium: 2-Arachidonoglycerol (endocannabinoid) interacts with endothelin-1. Circulation Research, 87(4), 323-327.