Cannabinoids and ceramide: two lipids acting hand-by-hand.
Cannabinoids, the active components of Cannabis sativa (marijuana) and their endogenous counterparts, exert their effects by binding to specific G-protein-coupled receptors that modulate adenylyl cyclase and ion channels. Recent research has shown that the CB1 cannabinoid receptor is also coupled to the generation of the lipid second messenger ceramide via two different pathways: sphingomyelin hydrolysis and ceramide synthesis de novo. Sustained ceramide accumulation in tumor cells mediates cannabinoid-induced apoptosis, as evidenced by in vitro and in vivo studies. This effect seems to be due to the impact of ceramide on key cell signalling systems such as the extracellular signal-regulated kinase cascade and the Akt pathway. These findings provide a new conceptual view on how cannabinoids act, and raise interesting physiological and therapeutic questions.
Velasco
Guillermo
G
Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, 28040 Madrid, Spain.
Galve-Roperh
Ismael
I
Sánchez
Cristina
C
Blázquez
Cristina
C
Haro
Amador
A
Guzmán
Manuel
M
D017209:Apoptosis / Q000502:physiology; D002186:Cannabinoids / Q000378:metabolism*; D002518:Ceramides / Q000096:biosynthesis / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008954:Models, Biological; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013109:Sphingomyelins / Q000378:metabolism
D002186:Cannabinoids; D002518:Ceramides; D043884:Receptor, Cannabinoid, CB1; D013109:Sphingomyelins; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases