Ceramide: a new second messenger of cannabinoid action.
Cannabinoids, the active components of Cannabis sativa (marijuana), and their endogenous counterparts exert their effects by binding to specific G(i/o)-protein-coupled receptors that modulate adenylyl cyclase, ion channels and extracellular signal-regulated kinases. Recent research has shown that the CB(1) cannabinoid receptor is coupled to the generation of the lipid second messenger ceramide via two different pathways: sphingomyelin hydrolysis, and ceramide synthesis de novo. Ceramide in turn mediates cannabinoid-induced apoptosis, as shown by in vitro and in vivo studies. These findings provide a new perspective on how cannabinoids act, and raise exciting physiological and therapeutic questions.
Guzmán
M
M
Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, 28040, Madrid, Spain. mgp@bbm1.ucm.es
Galve-Roperh
I
I
Sánchez
C
C
D000818:Animals; D002186:Cannabinoids / Q000378:metabolism / Q000494:pharmacology*; D002518:Ceramides / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D051381:Rats; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology*
D002186:Cannabinoids; D002518:Ceramides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug