Endogenous cannabinoid ligands — chemical and biological studies

Mechoulam, Raphael; Shabat, Sheer; Hanŭs, L; Fride, Ester; Vogel, Zvi; Bayewitch, Michael; Šulcová, Alexandra

doi:10.1016/0929-7855(96)01507-6

Cited by 51 publications

(32 citation statements)

References 16 publications

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“…The identification of the major active constituent of marijuana, Δ 9 -THC [2], followed by the biochemical and pharmacological characterization of the cannabinoid receptors [3,4], provided a solid foundation and opened a new perspectives for the study of this neurochemical system [5]. Moreover, the isolation of an endogenous ligand of cannabinoid receptors -anandamide, description of its synthesis and metabolic pathways indicated for the existence of an endocannabinergic system [4,6].…”

Section: Introductionmentioning

confidence: 99%

Cannabinoids enhance gastric X/A-like cells activity.

Zbucki

Sawicki²,

Hryniewicz³

et al. 2008

Folia Histochem Cytobiol.

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It has been reported that cannabinoids may cause overeating in humans and in laboratory animals. Although, endogenous cannabinoids and their receptors (CB1) have been found in the hypothalamus, and recently also in gastrointestinal tract, the precise mechanism of appetite control by cannabinoids remains unknown. Recently, ghrelin -a hormone secreted mainly from the stomach X/A-like cells was proposed to be an appetite stimulating agent. The aim of this study was the evaluation of the influence of a single ip injection of a stable analogue of endogenous cannabinoid -anandamide, R-(+)-methanandamide (2.5 mg/kg) and CP 55,940 (0.25 mg/kg), an exogenous agonist of CB1 receptors, on ghrelin plasma concentration and on ghrelin immunoreactivity in the gastric mucosa of male Wistar rats. Four hours after a single injection of both cannabinoids or vehicle, the animals were anaesthetized and blood was taken from the abdominal aorta to determinate plasma ghrelin concentration by RIA. Subsequently, the animals underwent resection of distal part of stomach. Immunohistochemical study of gastric mucosa, using the EnVision method and specific monoclonal antybodies against ghrelin was performed. The intensity of ghrelin immunoreactivity in X/A-like cells was analyzed using Olympus Cell D image analysis system. The attenuation of ghrelin-immunoreactivity of gastric mucosa, after a single injection of R-(+)-methanandamide and CP 55,940 was accompanied by a significant increase of ghrelin plasma concentration. These results indicate that stimulation of appetite exerted by cannabinoids may be connected with an increase of ghrelin secretion from gastric X/A-like cells.

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Section: Introductionmentioning

confidence: 99%

Cannabinoids enhance gastric X/A-like cells activity.

Zbucki

Sawicki²,

Hryniewicz³

et al. 2008

Folia Histochem Cytobiol.

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“…The only known signaling lipid containing an arachidonyl ester as a structural feature is the endocannabinoid, 2-arachidonyl glycerol (25). Cannabinoids, such as D…”

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confidence: 99%

Cannabinoid (CB2) receptor deficiency reduces the susceptibility of macrophages to oxidized LDL/oxysterol-induced apoptosis

Freeman-Anderson

Pickle

Netherland

et al. 2008

Journal of Lipid Research

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Macrophage apoptosis is an important process in the pathophysiology of atherosclerosis. Oxidized lowdensity lipoproteins (OxLDL) are a major component of lesions and potently induce macrophage apoptosis. Cannabinoid receptor 2 (CB2), the predominant macrophage cannabinoid receptor, modulates several macrophage processes associated with ongoing atherosclerosis; however, the role of CB2 in macrophage apoptosis is unknown. To determine if CB2 influences a macrophage apoptotic pathway relevant to atherosclerosis, we examined the effect of CB2 deficiency on OxLDL-induced macrophage apoptosis. In situ terminal transferase-mediated dUTP nick end labeling (TUNEL) analysis of resident peritoneal macrophages detected significantly fewer apoptotic CB2 2/2 macrophages than CB21/1 macrophages after incubation with OxLDL (27.9 6 4.7% vs. 61.9 6 8.5%, P , 0.001) or 7-ketocholesterol (7KC) (18.9 6 10.5% vs. 54.1 6 6.9%, P , 0.001), an oxysterol component of OxLDL. Caspase-3 activity; proteolytic conversion of procaspase-3; and cleavage of a caspase-3 substrate, PARP, were also diminished in 7KC-treated CB2 2/2 macrophages. Furthermore, the deactivation of the prosurvival kinase, Akt, in response to 7KC was impaired in CB2 2/2 macrophages. These results suggest that CB2 expression increases the susceptibility of macrophages to OxLDLinduced apoptosis, in part, by modulating the effect of oxysterols on the Akt survival pathway and that CB2 may influence atherosclerosis by modulating lesional macrophage apoptosis.

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“…In general, the affinity of anandamide for cannabinoid receptors is only ¼ to ½ the affinity displayed by  9 -THC, these differences being related to the cells or tissues used in those studies as well as with the other experimental conditions (Smith et al , 1994). Anandamide mimics  9 -THC action since it binds to both receptor subtypes, CB1 and CB2, and has a similar pharmacological activity, despite having little power to exert some effects (Fride & Mechoulam, 1993;Howlett , 1995;Mechoulam & Hanus, 1996;Pertwee 1995). This ligand was found in several regions of the human brain (hippocampus, striatum and cerebellum) where CB1 receptors are abundant, suggesting the involvement of endogenous cannabinoids in the brain functions controlled by these areas.…”

Section: Endogenous Cannabinoidsmentioning

confidence: 99%