Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P21554 (cannabinoid receptor)
 3,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present review summarizes the recent work carried out by our group on the link between signal transduction pathways and metabolic regulation systems as affected by cannabinoids. In cells such as astrocytes and lymphocytes, which express cannabinoid receptors, physiologically relevant doses of cannabinoids induce a remarkable metabolic stimulation as determined e.g. by enhanced glucose utilization. Studies performed in astrocytes show that the cannabinoid-evoked stimulation of glucose metabolism is independent of adenylyl cyclase inhibition, and seems to rely on the cascade CB1 cannabinoid receptor --> Sphingomyelin breakdown --> Ceramide --> Raf-1 --> Mitogen-activated protein kinase (MAPK) --> Glucose utilization. A role for phosphoinositide 3'-kinase in the stimulation of glucose utilization by cannabinoids is also put forward. In addition, ceramide generated upon CB1 cannabinoid receptor activation may enhance ketone body production by astrocytes independently of MAPK. Anandamide has also been shown to exert metabolic effects in hepatocytes, cells that do not express cannabinoid receptors. The biological role of cannabinoids as modulators of metabolism is as yet unclear.
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PMID:Effects of cannabinoids on energy metabolism. 1046 66

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.
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PMID:Ceramide: a new second messenger of cannabinoid action. 1116 67