Cannabinoid CB1 receptors of the parabrachial nucleus in selective modulation of various diets: A comparison with opioids.
0
Citation
0
Reference
10
Related Paper
Keywords:
DAMGO
μ-opioid receptor
Endocannabinoids are lipid mediators, enzymatically synthesized and hydrolyzed, that bind cannabinoid receptors. Together with their receptors and metabolic enzymes, they form the "endocannabinoid system" (ECS). Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are the main endocannabinoids studied in testis. In this study, using the first wave of spermatogenesis as an in vivo model to verify the progressive appearance of germ cells in seminiferous tubules [i.e., spermatogonia, spermatocytes, and spermatids], we analyzed the expression of the main enzymes and receptors of ECS in rat testis. In particular, the expression profile of the main enzymes metabolizing AEA and 2-AG as well as the expression of cannabinoid receptors, such as CB1 and CB2, and specific markers of mitotic, meiotic, and post-meiotic germ cell appearance or activities have been analyzed by RT-PCR and appropriately correlated. Our aim was to envisage a relationship between expression of ECS components and temporal profile of germ cell appearance or activity as well as among ECS components. Results show that expression of ECS components is related to germ cell progression. In particular, CB2 and 2-AG appear to be related to mitotic/meiotic stages, while CB1 and AEA appear to be related to spermatogonia stem cells activity and spermatids appearance, respectively. Our data also suggest that a functional interaction among ECS components occurs in the testis. Indeed, in vitro-incubated testis show that AEA-CB2 activity affects negatively monoacylglycerol-lipase levels via upregulation of CB1 suggesting a CB1/CB2-mediated relationship between AEA and 2-AG. Finally, we provide the first evidence that CB1 is present in fetal gonocytes, during mitotic arrest.
Anandamide
Cite
Citations (15)
Anandamide
Cite
Citations (1)
The endocannabinoid system is constituted by the endocannabinoid receptors (CB1 and CB2), by the endocannabinoids and the machinery for their biosynthesis and metabolism. Cannabinoid receptors have been localized in the central and peripheral nervous system as well as on cells of the immune system but recently they are discovered at epidermis and dermis1. The endocannabinoid system has been involved in different physiological processes, in particular many works in animal models have discovered an antinociceptive activities in inflammatory state and chronic inflammatory disease. Those findings suggest the possibility that the endocannabinoid system interacts with different cells so it will be interesting to provide a description of endocannabinoid receptors distribution. Immunohistochemical and molecular investigation for CB1 and CB2 localization was carried out in human skin and subcutaneous tissue and direct analysis on fibroblasts isolated from deep fascia2 and subcutaneous tissue of human and rat samples. The majority of endocannabinoid receptors were found in the keratinocytes of skin and mast cells close to subcutaneous adipose tissue, whilst in the deep fascia the presence is scarse. The CB2 receptors were more frequently highlighted respect to CB1 receptors. The abundant distribution of cannabinoid receptors on skin, mast cells and subcutaneous tissue provides implications for an anti-inflammatory, and this suggests more studies to evaluate the therapeutic potential of endocannabinoids.
Cite
Citations (0)
The endocannabinoid system consists of cannabinoid CB 1 and CB 2 receptors, of endogenous agonists for these receptors known as ‘endocannabinoids’, and of processes responsible for endocannabinoid biosynthesis, cellular uptake and metabolism. There is strong evidence first, that this system up-regulates in certain disorders as indicated by an increased release of endocannabinoids onto their receptors and/or by increases in the expression levels or coupling efficiency of these receptors, and second, that this up-regulation often appears to reduce or abolish unwanted effects of these disorders or to slow their progression. This discovery has raised the possibility of developing a medicine that enhances up-regulation of the endocannabinoid system associated with these disorders by inhibiting the cellular uptake or intracellular metabolism of an endocannabinoid following its ‘autoprotective’ endogenous release. For inhibition of endocannabinoid metabolism, research has focused particularly on two highly investigated endocannabinoids, anandamide and 2-arachidonoyl glycerol, and hence on inhibitors of the main anandamide-metabolising enzyme, fatty acid amide hydrolase (FAAH), and of the main 2-arachidonoyl glycerol-metabolising enzyme, monoacylglycerol (MAG) lipase. The resulting data have provided strong preclinical evidence that selective FAAH and MAG lipase inhibitors would ameliorate the unwanted effects of several disorders, when administered alone or with a cyclooxygenase inhibitor, and that the benefit-to-risk ratio of a FAAH inhibitor would exceed that of a MAG lipase inhibitor or dual inhibitor of FAAH and MAG lipase. Promising preclinical data have also been obtained with inhibitors of endocannabinoid cellular uptake. There is now an urgent need for clinical research with these enzyme and uptake inhibitors.
Cite
Citations (94)
Lateral parabrachial nucleus
μ-opioid receptor
Pons
Cite
Citations (19)
Anandamide
Cite
Citations (151)
Rimonabant
2-Arachidonoylglycerol
Cite
Citations (1)
A bstract : This review presents the remarkable research during the past several years indicating that some of the pharmacological and behavioral effects of alcohol, including alcohol drinking and alcohol‐preferring behavior, are mediated through one of the most abundant neurochemical systems in the central nervous system, the endocannabinoid signaling system . The advances, with the discovery of specific receptors and the existence of naturally occurring cannabis‐like substances in the mammalian system and brain, have helped in understanding the neurobiological basis for drugs of abuse, including alcoholism. The cDNA and genomic sequences encoding G‐protein‐coupled cannabinoid receptors (CB1 and CB2) from several species have now been cloned. This has facilitated discoveries of endogenous ligands (endocannabinoids). To date, two fatty acid derivatives characterized to be arachidonylethanolamide and 2‐arachidonylglycerol have been isolated from both nervous and peripheral tissues. Both these compounds have been shown to mimic the pharmacological and behavioral effects of Δ 9 ‐tetrahydrocannabinol, the psychoactive component of marijuana. The involvement of the endocannabinoid signaling system in tolerance development to drugs of abuse, including alcohol, were unknown until recently. Studies from our laboratory demonstrated for the first time the downregulation of CB1 receptor function and its signal transduction by chronic alcohol. The observed downregulation of CB1 receptor binding and its signal transduction results from the persistent stimulation of receptors by the endogenous CB1 receptor agonists arachidonylethanolamide and 2‐arachidonylglycerol, the synthesis of which is increased by chronic alcohol treatment. The deletion of CB1 receptor has recently been shown to block voluntary alcohol intake in mice, which is consistent with our previous findings where the DBA/2 mice known to avoid alcohol intake had significantly reduced brain CB1 receptor function. These findings suggest a role for the CB1 receptor gene in excessive alcohol drinking behavior and development of alcoholism. Ongoing investigations may lead to the development of potential therapeutic agents to modulate the endocannabinoid signaling system, which will be helpful for the treatment of alcoholism.
GPR18
Neurochemical
Cite
Citations (62)
Anandamide
Cite
Citations (72)
Abstract Stemming from the centuries‐old and well known effects of Cannabis on intestinal motility and secretion, research on the role of the endocannabinoid system in gut function and dysfunction has received ever increasing attention since the discovery of the cannabinoid receptors and their endogenous ligands, the endocannabinoids. In this article, some of the most recent developments in this field are discussed, with particular emphasis on new data, most of which are published in Neurogastroenterology & Motility , on the potential tonic endocannabinoid control of intestinal motility, the function of cannabinoid type‐1 (CB1) receptors in gastric function, visceral pain, inflammation and sepsis, the emerging role of cannabinoid type‐2 (CB2) receptors in the gut, and the pharmacology of endocannabinoid‐related molecules and plant cannabinoids not necessarily acting via cannabinoid CB1 and CB2 receptors. These novel data highlight the multi‐faceted aspects of endocannabinoid function in the GI tract, support the feasibility of the future therapeutic exploitation of this signaling system for the treatment of GI disorders, and leave space for some intriguing new hypotheses on the role of endocannabinoids in the gut.
Cite
Citations (23)