scholarly journals PUFA-derived endocannabinoids: an overview

2013 ◽  
Vol 72 (4) ◽  
pp. 451-459 ◽  
Author(s):  
Maria Grazia Cascio
Keyword(s):  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
Significant Progress ◽  
Intracellular Space ◽  
Step Process ◽  
Intracellular Degradation ◽  
Chain Pufa ◽  
Pathological Conditions ◽  
Long Chain

Following on from the discovery of cannabinoid receptors, of their endogenous agonists (endocannabinoids) and of the biosynthetic and metabolic enzymes of the endocannabinoids, significant progress has been made towards the understanding of the role of the endocannabinoid system in both physiological and pathological conditions. Endocannabinoids are mainly n-6 long-chain PUFA (LCPUFA) derivatives that are synthesised by neuronal cells and inactivated via a two-step process that begins with their transport from the extracellular to the intracellular space and culminates in their intracellular degradation by hydrolysis or oxidation. Although the enzymes responsible for the biosynthesis and metabolism of endocannabinoids have been well characterised, the processes involved in their cellular uptake are still a subject of debate. Moreover, little is yet known about the roles of endocannabinoids derived from n-3 LCPUFA such as EPA and DHA. Here, I provide an overview of what is currently known about the mechanisms for the biosynthesis and inactivation of endocannabinoids, together with a brief analysis of the involvement of the endocannabinoids in both food intake and obesity. Owing to limited space, recent reviews will be often cited instead of original papers.

scholarly journals Anandamide elevation in cerebrospinal fluid in initial prodromal states of psychosis

2009 ◽  
Vol 194 (4) ◽  
pp. 371-372 ◽  
Author(s):  
Dagmar Koethe ◽  
Andrea Giuffrida ◽  
Daniela Schreiber ◽  
Martin Hellmich ◽  
Frauke Schultze-Lutter ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
High Performance ◽  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
Structural Analog ◽  
Protective Role ◽  
Lipid Binding ◽  
Liquid Chromatograph ◽  
Early Schizophrenia

SummaryAnandamide is a bioactive lipid binding to cannabinoid receptors. A homeostatic role for anandamide has been suggested in schizophrenia. We investigated its role in initial prodromal states of psychosis. We measured the levels of anandamide and its structural analog oleoylethanolamide in cerebrospinal fluid and serum of patients in the initial prodromal state (n=27) alongside healthy volunteers (n=81) using high-performance liquid chromatograph/mass spectrometry. Cerebrospinal anandamide levels in patients were significantly elevated. Patients with lower levels showed a higher risk for transiting to psychosis earlier. This anandamidergic up-regulation in the initial prodromal course may suggest a protective role of the endocannabinoid system in early schizophrenia.

scholarly journals The Endocannabinoid System Contributes to Electroacupuncture Analgesia

2021 ◽  
Vol 14 ◽  
Author(s):  
Iona J. MacDonald ◽  
Yi-Hung Chen
Keyword(s):  
Cognitive Processes ◽  
Cannabinoid Receptors ◽  
Scientific Evidence ◽  
Antinociceptive Effect ◽  
Synthetic Cannabinoids ◽  
Behavioral Responses ◽  
Endocannabinoid System ◽  
Extensive Involvement ◽  
Effective Analgesia

The extensive involvement of the endocannabinoid system (ECS) in vital physiological and cognitive processes of the human body has inspired many investigations into the role of the ECS and drugs, and therapies that target this system and its receptors. Activation of cannabinoid receptors 1 and 2 (CB1 and CB2) by cannabinoid treatments, including synthetic cannabinoids, alleviates behavioral responses to inflammatory and neuropathic pain. An increasing body of scientific evidence details how electroacupuncture (EA) treatments achieve effective analgesia and reduce inflammation by modulating cannabinoid signaling, without the adverse effects resulting from synthetic cannabinoid administration. CB1 receptors in the ventrolateral area of the periaqueductal gray are critically important for the mechanisms of the EA antinociceptive effect, while peripheral CB2 receptors are related to the anti-inflammatory effects of EA. This review explores the evidence detailing the endocannabinoid mechanisms involved in EA antinociception.

Peripheral analgesia involves cannabinoid receptors

2018 ◽  
Author(s):  
Julie Desroches
Keyword(s):  
Cannabinoid Receptors ◽  
Receptor Gene ◽  
Endocannabinoid System ◽  
Cb1 Receptor ◽  
Pain Modulation ◽  
Cb1 Receptors ◽  
Gene Encoding ◽  
Cannabinoid Type 1 Receptor ◽  
Peripheral Analgesia

This landmark paper by Agarwal and colleagues was published in 2007, when the exact contribution of the activation of the cannabinoid type 1 receptor (CB1) receptors expressed on the peripheral terminals of nociceptors in pain modulation was still uncertain. At that time, while it was clearly demonstrated that the central nervous system (CNS) was involved in the antinociceptive effects induced by the activation of the CB1 receptor, many strains of mice in which the gene encoding the CB1 receptor was deleted by conditional mutagenesis were used to study the specific role of these receptors in pain. Creating an ingenious model of genetically modified mice with a conditional deletion of the CB1 receptor gene exclusively in the peripheral nociceptors, Agarwal and colleagues were the first to unequivocally demonstrate the major role of this receptor in the control of pain at the peripheral level. In fact, these mutant mice lacking CB1 receptors only in sensory neurons (those expressing the sodium channel Nav1.8) have been designed to highlight that CB1 receptors on nociceptors, and not those within the CNS, constitute an important target for mediating local or systemic (but not intrathecal) cannabinoid analgesia. Overall, they have clarified the anatomical locus of cannabinoid-induced analgesia, highlighted the potential significance of peripheral CB1-mediated cannabinoid analgesia, and revealed important insights into how the peripheral endocannabinoid system works in controlling both inflammatory pain and neuropathic pain.

103 Characterization of the receptors of the endocannabinoid system in equine sperm: Possible role of anandamide in sperm function

2021 ◽  
Vol 33 (2) ◽  
pp. 159
Author(s):  
C. Arroyo-Salvo ◽  
R. Lottero ◽  
A. Gambini ◽  
S. Perez Martinez
Keyword(s):  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
Sperm Capacitation ◽  
Phosphorylated Proteins ◽  
Middle Piece ◽  
Cryopreserved Sperm ◽  
Principal Piece ◽  
Post Hoc

Conventional IVF in horses remains challenging. In particular, stallion sperm fails to penetrate the zona pellucida, possibly due to incomplete invitro sperm capacitation. Therefore, there is a need to elucidate, in horses, molecules with a proven role during capacitation in other mammals. Our laboratory has described the relevance of the endocannabinoid system in capacitation of bovine and murine sperm. We reported that anandamide (AEA), an endocannabinoid present in follicular and oviducal fluids, induced capacitation-associated events. The aims of this work were to characterise the localization of cannabinoid receptors in equine sperm and to evaluate the effects of AEA on levels of tyrosine-phosphorylated proteins (pY) and substrates phosphorylated by protein kinase A (pPKA). Both cannabinoid receptors (CB1, CB2, TRPV1) and pPKA and pY were localised in sperm by indirect immunofluorescence. Sperm (15×106mL−1) were incubated, at 38.5°C in air, in modified Tyrode’s-albumin-lactate-pyruvate (TALP) with 25mM NaHCO3, 5mM dextrose and 1mgmL−1 polyvinyl alcohol (PVA; TALP-Bic-PVA) or TALP-Bic-PVA supplemented with AEA (0.1, 1, 10, 100nM, and 1µM) for 4h. After incubation, Western blot was used to determine levels of pY and pPKA in 4.5×106 sperm. Cryopreserved sperm samples from three stallions were evaluated. The normality of data distributions and homoscedasticity were verified with the Shapiro-Wilk and Levene tests, respectively. Data were analysed by one-way ANOVA and Bonferroni post hoc test, with P<0.05 considered significant. Based on immunofluorescence, CB1 was mainly localised in the post-acrosomal region and flagellum (93.4%±5.5, mean±s.d.), CB2 in the post-acrosomal region and middle piece (89.9%±28.3), and TRPV1 in the post-acrosomal region and flagellum (89.3%±9). Sperm positive for pPKA had fluorescence in the middle piece and principal piece of the flagellum. Incubation with 1nM AEA for 4h induced a 61% increase in pPKA levels compared with TALP-Bic-PVA medium alone, with no induction of pY levels in any treatment. In conclusion, cannabinoid receptors were present in equine sperm, and incubation with AEA induced an increase in PKA activity, an essential event associated with sperm capacitation. To our knowledge, this was the first report describing the presence of receptors of the endocannabinoid system in equine sperm and the potential role of AEA in the acquisition of sperm fertilizing ability.

scholarly journals Role of endocannabinoid system in the pathogenesis of obesity: how can we help a patient? From theory to practice

2020 ◽  
Vol 4 (6) ◽  
pp. 382-389
Author(s):  
V.A. Dudareva ◽  
◽  
M.L. Maksimov ◽  
I.G. Djadikova ◽  
A.A. Zveginceva ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Endocannabinoid System ◽  
Medical Society ◽  
Cannabinoid Receptor 1 ◽  
Peripheral Tissues ◽  
Theory To Practice

Obesity that results in various metabolic disorders is one of the central concerns of modern healthcare system. Only 4% to 5% of patients with metabolic syndrome achieve favorable outcomes without any additional pharmacotherapy. Therefore, many patients require weight-loss drugs in addition to non-pharmacological treatments. The endocannabinoid system and the drugs that affect its functions receive a widespread attention of medical society due to its effects on behavioral and cerebral functions and its potential use as a therapeutic “target” in various peripheral and neurological psychiatric disorders. Among known to date cannabinoid receptors, type 1 receptors play a role in the development of obesity. It was demonstrated that the blockade of these receptors in the hypothalamus reduces appetite, inhibits adipocyte activation in peripheral tissues, prevents lipogenesis, and increases the level of adiponectin. The result is the decreased levels of atherogenic lipoproteins and improved insulin resistance. This article addresses the results of fundamental and clinical studies on Dietressa, a drug composed of affine-purified antibodies to cannabinoid receptor 1. Case report of a patient with obesity that analyzes pharmaceutical and non-pharmaceutical treatment approaches is described.KEYWORDS: obesity, metabolic syndrome, diet, endocannabinoid system, cannabinoids, cannabinoid receptors, affine-purified antibodies.FOR CITATION: Dudareva V.A., Maksimov M.L., Djadikova I.G. et al. Role of endocannabinoid system in the pathogenesis of obesity: how can we help a patient? From theory to practice. Russian Medical Inquiry. 2020;4(6):382–389. DOI: 10.32364/2587-6821-2020-4-6-382-389.

scholarly journals Neuroprotection by Micronutrients and Cannabidiol (CBD) in Neurodegenerative Diseases

2020 ◽  
pp. 1-10
Author(s):  
Kedar N. Prasad ◽  
Kedar N. Prasad
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Neurodegenerative Diseases ◽  
Glutamate Receptors ◽  
Clinical Studies ◽  
Cannabinoid Receptors ◽  
Neurological Diseases ◽  
Endocannabinoid System ◽  
Protective Proteins

The major objectives of this review are to elucidate the role of antioxidants and cannabidiol (CBD) in reducing oxidative stress, inflammation, and glutamate levels, which contribute to the pathogenesis of human neurological diseases. Antioxidants act by: (a) donation of electrons to molecules with unpaired electrons to neutralize them, (b) activation of ROS-resistant Nrf2 to enhance the levels of antioxidant enzymes, (c) restoration of deficiency of antioxidants to normal levels, (d) alterations in the expression of microRNAs, which guide their respective mRNAs to translate protective proteins, and (e) prevention of the release and toxicity of glutamate. CBD acts by: (a) activating endocannabinoid system, which consists of anandamide and archidonoylglycerol, cannabinoid receptors CB1R and CB2R, and their synthesizing and degrading enzymes, (b) acting as an agonist to non-cannabinoid receptors, such as dopamine, serotonin, and adenosine, (c) acting as an inhibitor of serotonin re-uptake, and (d) acting as an antagonist to glutamate receptors. Since antioxidants and CBD act primarily by different mechanisms, it is proposed that combination of the two may be more effective than either individually. No review on this topic has been published. Pre-clinical and clinical studies are suggested to test the efficacy of proposed combination in selected neurodegenerative diseases.

scholarly journals The Role of the Endocannabinoid System in the Gynaecological Malignancy

2018 ◽  
Author(s):  
Flavio Grauso ◽  
Raffaele Autiero ◽  
Giuseppe R. Lannino ◽  
Brunella Zizolfi ◽  
Ciro Perone ◽  
...  
Keyword(s):  
Female Genital Tract ◽  
Endocannabinoid System ◽  
Sex Steroid Hormone ◽  
Fatty Acid Derivatives ◽  
Search Terms ◽  
Pathological Conditions ◽  
Gynaecological Malignancy ◽  
Potential Use ◽  
Female Genital

Background: The endocannabinoid system (ECS) is a very heterogeneous array consisting of many proteins like ligands, enzymes and receptors synthetized in various tissues and immunity cells. The main endogenous ligands are unsaturated fatty acid derivatives like anandamide(AEA), 2-arachidonoylglycerol(2-AG), but many others are under study. Endocannabinoids are involved in both physiological and pathological conditions. ECS plays an important role in the regulation of main processes which lead to cancer and also in sex steroid hormone-related cancers.Methods: With focus on gynaecological cancers, main papers and review articles, up to April 2018, on the role of the ECS, were acquired by PubMed searches using the search terms: ‘cancer’, ‘cannabinoid’, ‘endocannabinoid’, ‘gynaecology’ and ‘malignancy’.Results: The review of recent literature data showed the involvement of the endocannabinoid system in numerous physiological and pathological conditions of the female genital tract up to the development of gynaecological malignancy as cervical, endometrial and ovarian cancer.Conclusions: The endocannabinoid system has an important role in antitumor actions involving different signalling receptor and receptor-independent pathways. It represents an exciting challenge to researchers for its potential use in diagnosis and treatment of all gynaecological malignancies

scholarly journals Distinctive Evidence Involved in the Role of Endocannabinoid Signalling in Parkinson’s Disease: A Perspective on Associated Therapeutic Interventions

2020 ◽  
Vol 21 (17) ◽  
pp. 6235
Author(s):  
Tapan Behl ◽  
Gagandeep Kaur ◽  
Simona Bungau ◽  
Rishabh Jhanji ◽  
Arun Kumar ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cannabinoid Receptors ◽  
Life Quality ◽  
Endocannabinoid System ◽  
Therapeutic Interventions ◽  
Diseased State ◽  
Preclinical And Clinical Studies ◽  
Signalling Systems

Current pharmacotherapy of Parkinson’s disease (PD) is symptomatic and palliative, with levodopa/carbidopa therapy remaining the prime treatment, and nevertheless, being unable to modulate the progression of the neurodegeneration. No available treatment for PD can enhance the patient’s life-quality by regressing this diseased state. Various studies have encouraged the enrichment of treatment possibilities by discovering the association of the effects of the endocannabinoid system (ECS) in PD. These reviews delineate the reported evidence from the literature on the neuromodulatory role of the endocannabinoid system and expression of cannabinoid receptors in symptomatology, cause, and treatment of PD progression, wherein cannabinoid (CB) signalling experiences alterations of biphasic pattern during PD progression. Published papers to date were searched via MEDLINE, PubMed, etc., using specific key words in the topic of our manuscript. Endocannabinoids regulate the basal ganglia neuronal circuit pathways, synaptic plasticity, and motor functions via communication with dopaminergic, glutamatergic, and GABAergic signalling systems bidirectionally in PD. Further, gripping preclinical and clinical studies demonstrate the context regarding the cannabinoid compounds, which is supported by various evidence (neuroprotection, suppression of excitotoxicity, oxidative stress, glial activation, and additional benefits) provided by cannabinoid-like compounds (much research addresses the direct regulation of cannabinoids with dopamine transmission and other signalling pathways in PD). More data related to endocannabinoids efficacy, safety, and pharmacokinetic profiles need to be explored, providing better insights into their potential to ameliorate or even regress PD.

scholarly journals Characterization of Endocannabinoid System and Interleukin Profiles in Ovine AEC: Cannabinoid Receptors Type-1 and Type-2 as Key Effectors of Pro-Inflammatory Response

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 1008 ◽  
Author(s):  
Luana Greco ◽  
Valentina Russo ◽  
Cinzia Rapino ◽  
Clara Di Germanio ◽  
Filomena Fezza ◽  
...  
Keyword(s):  
Immune Modulation ◽  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
Middle Stage ◽  
Selective Agonists ◽  
Anti Inflammatory

Amniotic epithelial cells (AEC) have been proposed as promising clinical candidates for regenerative medicine therapies due to their immunomodulatory capacity. In this context, the endocannabinoid system (ECS) has been identified as mediating the immune-stem cell dialogue, even if no information on AEC is available to date. Therefore, this study was designed to assess whether ECS is involved in tuning the constitutive and lipopolysaccharide (LPS)-induced ovine AEC anti-inflammatory and pro-inflammatory interleukin (IL-10, IL-4, and IL-12) profiles. Firstly, interleukins and ECS expressions were studied at different stages of gestation. Then, the role of cannabinoid receptors 1 and 2 (CB1 and CB2) on interleukin expression and release was investigated in middle stage AEC using selective agonists and antagonists. AEC displayed a degradative more than a synthetic endocannabinoid metabolism during the early and middle stages of gestation. At the middle stage, cannabinoid receptors mediated the balance between pro-inflammatory (IL-12) and anti-inflammatory (IL-4 and IL-10) interleukins. The activation of both receptors mediated an overall pro-inflammatory shift—CB1 reduced the anti-inflammatory and CB2 increased the pro-inflammatory interleukin release, particularly after LPS stimulation. Altogether, these data pave the way for the comprehension of AEC mechanisms tuning immune-modulation, crucial for the development of new AEC-based therapy protocols.

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