Human brain capillary endothelium: 2-arachidonoglycerol (endocannabinoid) interacts with endothelin-1.
In brain, the regulatory mechanism of the endothelial reactivity to nitric oxide and endothelin-1 may involve Ca(2+), cytoskeleton, and vasodilator-stimulated phosphoprotein changes mediated by the cGMP/cGMP kinase system.(1) 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 Ca(2+) 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 Ca(2+)-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.
Chen
Y
Y
Stroke Branch, National Institute of Neurological Disorders and Stroke,National Institutes of Health, Bethesda, MD 20892-4128, USA.
McCarron
R M
RM
Ohara
Y
Y
Bembry
J
J
Azzam
N
N
Lenz
F A
FA
Shohami
E
E
Mechoulam
R
R
Spatz
M
M
D000199:Actins / Q000378:metabolism; D001095:Arachidonic Acids; D001921:Brain / Q000098:blood supply* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators; D002196:Capillaries / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D019332:Endothelin-1 / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D005989:Glycerides / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008840:Microfilament Proteins; D018377:Neurotransmitter Agents / Q000378:metabolism / Q000494:pharmacology*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology; D000098662:Vasodilator-Stimulated Phosphoprotein
D000199:Actins; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D015815:Cell Adhesion Molecules; D063388:Endocannabinoids; D019332:Endothelin-1; D005989:Glycerides; D008840:Microfilament Proteins; D018377:Neurotransmitter Agents; D010750:Phosphoproteins; D014665:Vasodilator Agents; D000098662:Vasodilator-Stimulated Phosphoprotein; C094503:glyceryl 2-arachidonate; D002118:Calcium