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

The effects of cannabinoids on metabolic pathways and signal transduction systems were studied in primary cultures of rat astrocytes. Delta9-Tetrahydrocannabinol (THC), the major active component of marijuana, increased the rate of glucose oxidation to CO2 as well as the rate of glucose incorporation into phospholipids and glycogen. These effects of THC were mimicked by the synthetic cannabinoid HU-210, and prevented by forskolin, pertussis toxin, and the CB1 receptor antagonist SR 141716. THC did not affect basal cAMP levels but partially antagonized the forskolin-induced elevation of intracellular cAMP concentration. THC stimulated p42/p44 mitogen-activated protein kinase (MAPK) activity, Raf-1 phosphorylation, and Raf-1 translocation to the particulate cell fraction. In addition, the MAPK inhibitor PD 098095 and the phosphoinositide 3-kinase inhibitors wortmannin and LY 294002 were able to antagonize the THC-induced stimulation of glucose oxidation to CO2, phospholipid synthesis and glycogen synthesis. The possible involvement of sphingomyelin breakdown in the metabolic effects of THC was studied subsequently. THC produced a rapid stimulation of sphingomyelin hydrolysis that was concomitant to an elevation of intracellular ceramide levels. This effect was prevented by SR 141716. Moreover, the cell-permeable ceramide analog D-erythro-N-octanoylsphingosine, as well as exogenous sphingomyelinase, were able in turn to stimulate MAPK activity, to increase the amount of Raf-1 bound to the particulate cell fraction, and to stimulate glucose metabolism. The latter effect was prevented by PD 098059 and was not additive to that exerted by THC. Results thus indicate that THC produces a cannabinoid receptor-mediated stimulation of astrocyte metabolism that seems to rely on sphingomyelin hydrolysis and MAPK stimulation.
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PMID:Involvement of sphingomyelin hydrolysis and the mitogen-activated protein kinase cascade in the Delta9-tetrahydrocannabinol-induced stimulation of glucose metabolism in primary astrocytes. 980 18

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 marihuana, exert a variety of effects in humans. Many of these effects are mediated by binding to two types of cannabinoid receptor, CB1 and CB2. Although CB1 is located mainly in the central nervous system, it may also be found in peripheral tissues. Here, we study the effect of cannabinoids in the production of nerve growth factor by the prostate tumor cell line PC-3. We show that addition of Delta(9)-tetrahydrocannabinol to PC-3 cells stimulated nerve growth factor production in a dose-dependent and time-dependent manner. Maximal effect was observed at 0.1 microM Delta(9)-tetrahydrocannabinol and 72 h of treatment. Stimulation was reversed by the CB1 antagonists AM 251 and SR 1411716A. Pre-treatment of cells with pertussis toxin also prevented the effect promoted by Delta(9)-tetrahydrocannabinol. These results indicate that Delta(9)-tetrahydrocannabinol stimulation of nerve growth factor production in these cells was mediated by the cannabinoid CB1 receptor. The implication of Raf-1 activation in the mode of action of Delta(9)-tetrahydrocannabinol is also suggested.
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PMID:delta(9)-Tetrahydrocannabinol increases nerve growth factor production by prostate PC-3 cells. Involvement of CB1 cannabinoid receptor and Raf-1. 1116 91

Cannabinoids exert a variety of physiological and pharmacological responses in humans through interaction with specific cannabinoid receptors. Cannabinoid receptors described to date belong to the seven-transmembrane-domain receptor superfamily and are coupled through the inhibitory G(i) protein to adenylyl cyclase inhibition. However, downstream signal transduction mechanisms triggered by cannabinoids are poorly understood. We examined here the involvement of the phosphoinositide 3-kinase (PI3K)/PKB pathway in the mechanism of action of cannabinoids in human prostate epithelial PC-3 cells. Cannabinoid receptors CB(1) and CB(2) are expressed in these cells, as shown by RT-PCR, Western blot and immunofluorescence techniques. Treatment of PC-3 cells with either Delta(9)-tetrahydrocannabinol (THC), the major psychoactive ingredient of marijuana, or R-(+)-methanandamide (MET), an analogue of the endogenous cannabinoid anandamide, increased phosphorylation of PKB in Thr308 and Ser473. The stimulation of PKB induced by cannabinoids was blocked by the two cannabinoid receptor antagonists, SR 141716 and SR 144528, and by the PI3K inhibitor LY 294002. These results indicate that activation of cannabinoid receptors in PC-3 cells stimulate the PI3K/PKB pathway. We further investigated the involvement of Raf-1/Erk activation in the mechanism of action of cannabinoid receptors. THC and MET induced translocation of Raf-1 to the membrane and phosphorylation of p44/42 Erk kinase, which was reversed by cannabinoid receptor antagonists and PI3K inhibitor. These results point to a sequential connection between cannabinoid receptors/PI3K/PKB pathway and Raf-1/Erk in prostate PC-3 cells. We also show that this pathway is involved in the mechanism of NGF induction exerted by cannabinoids in PC-3 cells.
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PMID:Activation of phosphoinositide 3-kinase/PKB pathway by CB(1) and CB(2) cannabinoid receptors expressed in prostate PC-3 cells. Involvement in Raf-1 stimulation and NGF induction. 1283 10