The endocannabinoid system: a general view and latest additions

Petrocellis, Luciano De; Cascio, Maria Grazia; Marzo, Vincenzo Di

doi:10.1038/sj.bjp.0705666

Cited by 429 publications

(379 citation statements)

References 100 publications

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“…12,13 Within the brain, ECs act as retrograde neurotransmitters (or messengers) that inhibit synaptic activity. 15 More recently, the EC system has also been shown to be an intercellular signalling system that plays an important role in various peripheral organs, especially those controlling energy metabolism.…”

Section: The Endocannabinoid Systemmentioning

confidence: 99%

“…7,10,11 Over the last two decades a new biochemical/physiological system, known as the endocannabinoid (EC) system, was discovered. 12,13 There is considerable evidence that the EC system plays a significant role in appetite drive and associated behaviours, but also in endocrine and metabolic regulation and energy balance. 14 Indeed, cannabinoid (CB) receptors, especially CB1 receptors, participate in the physiological modulation of many central and peripheral functions.…”

Section: Introductionmentioning

confidence: 99%

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Cannabinoid-1 receptor antagonists in type-2 diabetes

Scheen

2007

Best Practice & Research Clinical Endocrinology & Metab

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Type-2 diabetes is closely related to abdominal obesity and is generally associated with other cardiometabolic risk factors, resulting in a risk of major cardiovascular disease. Several animal and human observations suggest that the endocannabinoid system is over-active in the presence of abdominal obesity and/or diabetes. Both central and peripheral endocannabinoid actions, via the activation of CB1 receptors, promote weight gain and associated metabolic changes. Rimonabant, the first selective CB 1 receptor blocker in clinical use, has been shown to reduce body weight, waist circumference, triglycerides, blood pressure, insulin resistance index and C-reactive protein levels, and to increase high-density lipoprotein (HDL) cholesterol and adiponectin concentrations in both non-diabetic and diabetic overweight/obese patients. In addition, a 0.5-0.7% reduction in HbA1c levels was observed in metformin-or sulphonylurea-treated patients with type-2 diabetes and in drugnaïve diabetic patients. Almost half of the metabolic changes, including HbA1c reduction, could not be explained by weight loss, suggesting that there are direct peripheral effects. Rimonabant was generally welltolerated, and the safety profile was similar in diabetic and non-diabetic patients, with a higher incidence of depressed mood disorders, nausea and dizziness. In conclusion, the potential role of rimonabant in overweight/obese patients with type-2 diabetes and at high risk of cardiovascular disease deserves much consideration.Keywords: rimonabant ; obesity ; type-2 diabetes ; cardiovascular risk ; CB 1 receptor blocker ; endocannabinoid system. Type-2 diabetes frequently coexists with a cluster of other cardiovascular and metabolic risk factors -including abdominal obesity, low high-density lipoprotein cholesterol (HDL-C), high triglycerides, elevated blood pressure and silent inflammation -and is considered to be a cardiovascular disease (CVD) risk equivalent. 1,2 Being overweight or obese -abdominally obese in particular -increases the risk of type-2 diabetes and CVD. [3][4][5] Yet individuals with type-2 diabetes often have more difficulty in losing weight and experience weight gain associated with most antidiabetic medications. 6,7 The treatment of multiple cardiovascular and metabolic riskfactors is central to the management of diabetic patients 1,2,5,8,9 , and the importance of weight management is well recognized in type-2 diabetes. 7,10,11 Over the last two decades a new biochemical/physiological system, known as the endocannabinoid (EC) system, was discovered. 12,13 There is considerable evidence that the EC system plays a significant role in appetite drive and associated behaviours, but also in endocrine and metabolic regulation and energy balance. 14 Indeed, cannabinoid (CB) receptors, especially CB1 receptors, participate in the physiological modulation of many central and peripheral functions. 14 The tremendous advances in the understanding of the molecular basis of CB activity 15 has encouraged many pharmaceutical companie...

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Section: The Endocannabinoid Systemmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cannabinoid-1 receptor antagonists in type-2 diabetes

Scheen

2007

Best Practice & Research Clinical Endocrinology & Metab

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“…A conserved endocannabinoid system has been identified in mammals and includes at least two G-protein coupled receptors (For review see (Petrocellis et al, 2004). The CB 1 receptor subtype is widely expressed, with particularly high levels in the hippocampus, cerebellum and basal ganglia, and mediates most CNS effects of cannabinoids (Herkenham et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Effect of social isolation on CB1 and D2 receptor and fatty acid amide hydrolase expression in rats

et al. 2008

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Rearing rats in isolation has been shown to produce behavioral and neurochemical alterations similar to those observed in psychoses such as schizophrenia. Also, a dysregulation in both the endocannabinoid and dopaminergic systems has been implicated in schizophrenia. The aim of this study was to determine if there are differences in CB 1 receptor and fatty acid amide hydrolase (FAAH) protein expression, as well as D 2 dopamine receptor expression in different brain regions in rats reared in different environmental conditions. Twenty-one day old male Sprague-Dawley rats were either reared in individual cages (isolated rats) or in group cages of 6 per cage (group housed rats) for 8 weeks. Quantitative fluorescence immunohistochemistry was performed on brain slices using antibodies specific to the CB 1 or D 2 receptor, or the enzyme FAAH. Raising rats in isolation led to a significant decrease in CB 1 receptor expression in the caudate putamen and the amygdala, a significant increase in FAAH expression in the caudate putamen and the nucleus accumbens core and shell, and no significant change in D 2 receptor expression in any region studied. These results indicate that the endocannabinoid system is altered in an animal model of aspects of psychosis. This implies that rearing rats under different housing conditions may provide new insight into the role of the endocannabinoid system in the development of psychoses.

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“…endocannabinoids ͉ lipids ͉ seedling growth ͉ signaling T he discovery of membrane receptors (cannabinoid receptors) in mammalian brain tissue that bind to marijuana's principal psychoactive compound, ⌬9-tetrahydrocannabinol, led to the establishment of the endocannabinoid signaling pathway as a key regulator of important neurological processes in animals (1). Central to endocannabinoid signaling are the N-acylethanolamines (NAEs), a group of fatty acids with amide linkages to ethanolamine.…”

mentioning

confidence: 99%

Manipulation of Arabidopsis fatty acid amide hydrolase expression modifies plant growth and sensitivity to N -acylethanolamines

Wang

Shrestha

Kilaru

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

158

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In vertebrates, the endocannabinoid signaling pathway is an important lipid regulatory pathway that modulates a variety of physiological and behavioral processes. N-Acylethanolamines (NAEs) comprise a group of fatty acid derivatives that function within this pathway, and their signaling activity is terminated by an enzyme called fatty acid amide hydrolase (FAAH), which hydrolyzes NAEs to ethanolamine and their corresponding free fatty acids. Bioinformatic approaches led to the identification of plant homologues of FAAH that are capable of hydrolyzing NAEs in vitro. To better understand the role of NAEs in plants, we identified T-DNA knockouts to Arabidopsis FAAH (AtFAAH; At5g64440) and generated plants overexpressing AtFAAH. Here we show that seeds of AtFAAH knockouts had elevated levels of endogenous NAEs, and seedling growth was hypersensitive to exogenously applied NAE. On the other hand, seeds and seedlings of AtFAAH overexpressors had lower endogenous NAE content, and seedlings were less sensitive to exogenous NAE. Moreover, AtFAAH overexpressors displayed enhanced seedling growth and increased cell size. AtFAAH expression and FAAH catalytic activity increased during seed germination and seedling growth, consistent with the timing of NAE depletion during seedling establishment. Collectively, our results show that AtFAAH is one, but not the only, modulator of endogenous NAE levels in plants, and that NAE depletion likely participates in the regulation of plant growth.endocannabinoids ͉ lipids ͉ seedling growth ͉ signaling

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The endocannabinoid system: a general view and latest additions

Cited by 429 publications

References 100 publications

Cannabinoid-1 receptor antagonists in type-2 diabetes

Cannabinoid-1 receptor antagonists in type-2 diabetes

Effect of social isolation on CB1 and D2 receptor and fatty acid amide hydrolase expression in rats

Manipulation of Arabidopsis fatty acid amide hydrolase expression modifies plant growth and sensitivity to N -acylethanolamines

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