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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

An investigation into the effects of endocannabinoids and the COX-2 metabolite of 2-Arachidonyl glycerol on bone cells

Ford, Lorna January 2009 (has links)
The effects of endocannabinoids on human, mouse and rabbit bone cells were investigated.  At high concentrations anandamide and 2-arachidonyl glycerol (2-AG) inhibited human osteoclast formation with no effects at lower concentrations. The inhibition was not attenuated by antagonists for the CB<sub>1</sub>, CB<sub>2</sub> or TRPV1 receptors, indicating a non-receptor mediated effect.  Conversely, anandamide and 2-AG increased mouse osteoclast formation.  The effect of anandamide was enhanced in cells from fatty acid amide hydrolase (FAAH)-null mice and abolished in cells from CB<sub>1/2</sub> knockout mice.  The effect of 2-AG was not eliminated in CB<sub>1/2</sub> knockout cells, indicating a non-CB<sub>1</sub>/CB<sub>2</sub> action.  The CB<sub>1</sub> antagonist, AM251, and the CB<sub>2</sub> antagonist, AM630, both inhibited mouse osteoclast formation.  These effects were not rescued in the CB<sub>1/2</sub>-knockout mouse cells.  Both anandamide and 2-AG stimulated actin ring formation and osteoclast activity in human and rabbit osteoclast.  This was prevented in the presence of AM630 but not AM251, indicating a CB<sub>2</sub>-mediated response.  The endocannabinoids and the cannabinoid receptor antagonists do not have a regulatory action on osteoblast activity. The effects of the novel cyclooxygenase-2 (COX-2) metabolite of 2-AG, prostaglandin E<sub>2</sub>-glycerol ester (PGE<sub>2</sub>-G), on human osteoclasts were examined.  Treatment with PGE<sub>2</sub>-G inhibited formation and ERK phosphorylation of human osteoclasts.  These effects were attenuated by a selective EP<sub>4</sub> antagonist and mimicked by PGE<sub>2</sub> alone, indicating that PGF<sub>2</sub>-G is rapidly metabolised into PGE<sub>2</sub> in human osteoclast cultures.  However, PGE<sub>2</sub>-G treatment elevated intracellular calcium levels in human osteoclasts, through a phospholipase C (PLC)- and IP<sub>3</sub>- dependent mechanism, indicative of a G-protein coupled receptor effect.  This was not mimicked by PGE<sub>2</sub>, or prevented by the EP<sub>4</sub> antagonist, but blocked by a putative PGE<sub>2</sub>-G receptor antagonist, PDA-94 indicating that PDA-94 may be a PGE<sub>2</sub>-G receptor antagonist.
2

An investigation into the effects of endocannabinoids and the COX-2 metabolite of 2-Arachidonyl glycerol on bone cells

Ford, Lorna. January 2009 (has links)
Thesis (Ph.D.)--Aberdeen University, 2009. / Title from web page (viewed on Oct. 8, 2009). Includes bibliographical references.

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