2‐Arachidonoyl glycerol potently induces cholecystokinin secretion in murine enteroendocrine STC ‐1 cells via cannabinoid receptor CB1

Lipids ◽  
2021 ◽  
Author(s):  
Keita Ochiai ◽  
Rina Hirooka ◽  
Masayoshi Sakaino ◽  
Shigeo Takeuchi ◽  
Tohru Hira
Keyword(s):  
Cannabinoid Receptor ◽  
Arachidonoyl Glycerol

scholarly journals Chemical probes to potently and selectively inhibit endocannabinoid cellular reuptake

2017 ◽  
Vol 114 (25) ◽  
pp. E5006-E5015 ◽  
Author(s):  
Andrea Chicca ◽  
Simon Nicolussi ◽  
Ruben Bartholomäus ◽  
Martina Blunder ◽  
Alejandro Aparisi Rey ◽  
...  
Keyword(s):  
Membrane Trafficking ◽  
Cannabinoid Receptor ◽  
Facilitated Diffusion ◽  
Chemical Probes ◽  
Analgesic Effects ◽  
Complex Process ◽  
Arachidonoyl Glycerol ◽  
The Brain

The extracellular effects of the endocannabinoids anandamide and 2-arachidonoyl glycerol are terminated by enzymatic hydrolysis after crossing cellular membranes by facilitated diffusion. The lack of potent and selective inhibitors for endocannabinoid transport has prevented the molecular characterization of this process, thus hindering its biochemical investigation and pharmacological exploitation. Here, we report the design, chemical synthesis, and biological profiling of natural product-derivedN-substituted 2,4-dodecadienamides as a selective endocannabinoid uptake inhibitor. The highly potent (IC50= 10 nM) inhibitorN-(3,4-dimethoxyphenyl)ethyl amide (WOBE437) exerted pronounced cannabinoid receptor-dependent anxiolytic, antiinflammatory, and analgesic effects in mice by increasing endocannabinoid levels. A tailored WOBE437-derived diazirine-containing photoaffinity probe (RX-055) irreversibly blocked membrane transport of both endocannabinoids, providing mechanistic insights into this complex process. Moreover, RX-055 exerted site-specific anxiolytic effects on in situ photoactivation in the brain. This study describes suitable inhibitors to target endocannabinoid membrane trafficking and uncovers an alternative endocannabinoid pharmacology.

scholarly journals The Endocannabinoid System of Animals

2019 ◽  
Author(s):  
Robert Silver
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabis Sativa ◽  
Cannabinoid Receptor ◽  
Mammalian Species ◽  
Endocannabinoid System ◽  
Precise Determination ◽  
Organ Systems ◽  
Protein Receptors ◽  
Ubiquitous System ◽  
Arachidonoyl Glycerol

The endocannabinoid system has been found to be pervasive in mammalian species. It has also been described in invertebrate species primitive as the Hydra. Insects apparently are devoid of this otherwise ubiquitous system that provides homeostatic balance to the nervous and immune systems, as well as many other organ systems. The endocannabinoid system (ECS) has been defined to consist of three parts: 1. Endogenous ligands, 2. G-protein coupled receptors (GPCRs), and 3. Enzymes to degrade and recycle the ligands. Two endogenous molecules have been identified as ligands in the ECS to date. These are the endocannabinoids: Anandamide (arachidonoyl ethanolamide) and 2-AG (2-arachidonoyl glycerol). Two G-coupled protein receptors have been described as part of this system, with other putative GPC being considered. Coincidentally, the phytochemicals produced in large quantities by the Cannabis sativa L plant, and in lesser amounts by other plants, can interact with this system as ligands. These plant-based cannabinoids are termed, phytocannabinoids. The precise determination of the distribution of cannabinoid receptors in animal species is an ongoing project, with the canine cannabinoid receptor distribution currently receiving the most interest in non-human animals.

scholarly journals Early Cannabinoid Exposure as a Source of Vulnerability to Opiate Addiction: A Model in Laboratory Rodents

1998 ◽  
Vol 1 ◽  
pp. 39-58 ◽  
Author(s):  
Miguel Navarro ◽  
Fernando Rodríguez de Fonseca
Keyword(s):  
Brain Function ◽  
Cannabis Sativa ◽  
Cannabinoid Receptor ◽  
Adult Brain ◽  
Opiate Abuse ◽  
Laboratory Rodents ◽  
Endogenous Cannabinoid ◽  
Arachidonoyl Glycerol ◽  
The Brain ◽  
Endogenous Cannabinoid System

Recent findings have identified an endogenous brain system mediating the actions of cannabis sativa preparations. This system includes the brain cannabinoid receptor (CB-1) and its endogenous ligands anandamide and 2-arachidonoyl-glycerol. The endogenous cannabinoid system is not only present in the adult brain, but is also active at early stages of brain development. Studies developed at our laboratory have revealed that maternal exposure to psychoactive cannabinoid results in neuro-developmental alterations. A model is proposed in which early Δ9-tetrahydrocannabinol (THC) exposure during critical developmental periods results in permanent alterations in brain function by either the stimulation of CB-1 receptors present during the development, or by the alterations in maternal glucocorticoid secretion. Those alterations will be revealed in adulthood after challenges either with drugs (i.e. opiates) or with environmental stressors (i.e. novelty). They will include a modified pattern of neuro-chemical, endocrine, and behavioral responses that might lead ultimately to inadaptation and vulnerability to opiate abuse.

scholarly journals The Endocannabinoid System of Animals

Animals ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 686 ◽  
Author(s):  
Robert J. Silver
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabis Sativa ◽  
Cannabinoid Receptor ◽  
Mammalian Species ◽  
Endocannabinoid System ◽  
Precise Determination ◽  
Organ Systems ◽  
Protein Receptors ◽  
Ubiquitous System ◽  
Arachidonoyl Glycerol

The endocannabinoid system has been found to be pervasive in mammalian species. It has also been described in invertebrate species as primitive as the Hydra. Insects, apparently, are devoid of this, otherwise, ubiquitous system that provides homeostatic balance to the nervous and immune systems, as well as many other organ systems. The endocannabinoid system (ECS) has been defined to consist of three parts, which include (1) endogenous ligands, (2) G-protein coupled receptors (GPCRs), and (3) enzymes to degrade and recycle the ligands. Two endogenous molecules have been identified as ligands in the ECS to date. The endocannabinoids are anandamide (arachidonoyl ethanolamide) and 2-AG (2-arachidonoyl glycerol). Two G-coupled protein receptors (GPCR) have been described as part of this system, with other putative GPC being considered. Coincidentally, the phytochemicals produced in large quantities by the Cannabis sativa L plant, and in lesser amounts by other plants, can interact with this system as ligands. These plant-based cannabinoids are termed phytocannabinoids. The precise determination of the distribution of cannabinoid receptors in animal species is an ongoing project, with the canine cannabinoid receptor distribution currently receiving the most interest in non-human animals.

scholarly journals Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of endocannabinoid signaling in the brain

2003 ◽  
Vol 163 (3) ◽  
pp. 463-468 ◽  
Author(s):  
Tiziana Bisogno ◽  
Fiona Howell ◽  
Gareth Williams ◽  
Alberto Minassi ◽  
Maria Grazia Cascio ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Developmental Change ◽  
Enzymatic Characterization ◽  
Temporal Regulation ◽  
Cb1 Cannabinoid Receptor ◽  
Wide Range ◽  
Dendritic Fields ◽  
Arachidonoyl Glycerol ◽  
The Brain

Diacylglycerol (DAG) lipase activity is required for axonal growth during development and for retrograde synaptic signaling at mature synapses. This enzyme synthesizes the endocannabinoid 2-arachidonoyl-glycerol (2-AG), and the CB1 cannabinoid receptor is also required for the above responses. We now report on the cloning and enzymatic characterization of the first specific sn-1 DAG lipases. Two closely related genes have been identified and their expression in cells correlated with 2-AG biosynthesis and release. The expression of both enzymes changes from axonal tracts in the embryo to dendritic fields in the adult, and this correlates with the developmental change in requirement for 2-AG synthesis from the pre- to the postsynaptic compartment. This switch provides a possible explanation for a fundamental change in endocannabinoid function during brain development. Identification of these enzymes may offer new therapeutic opportunities for a wide range of disorders.

Cannabinoids stimulate prostaglandin production by human gestational tissues through a tissue- and CB1-receptor-specific mechanism

2008 ◽  
Vol 294 (2) ◽  
pp. E352-E356 ◽  
Author(s):  
Murray D. Mitchell ◽  
Timothy A. Sato ◽  
Anderson Wang ◽  
Jeffrey A. Keelan ◽  
Anna P. Ponnampalam ◽  
...  
Keyword(s):  
Preterm Labor ◽  
Potential Role ◽  
Cannabinoid Receptor ◽  
Cb1 Receptor ◽  
Specific Mechanism ◽  
Prostaglandin Production ◽  
Membrane Rupture ◽  
Cox 2 ◽  
Gestational Tissues ◽  
Arachidonoyl Glycerol

Endocannabinoids have been implicated in the mechanisms of implantation, maintenance of pregnancy, and parturition in women. Intrauterine prostaglandin production and actions are also critical in each of these mechanisms. Hence, we have evaluated the effects of cannabinoids on prostaglandin biosynthesis by human gestational membranes. Explants of term amnion and choriodecidua were established and treated with the endogenous endocannabinoids 2-arachidonoyl glycerol and anandamide, as well as the synthetic cannabinoid CP55,940, to determine their ability to modulate PGE2 production. The explants were also treated with CP55,940 in the presence of either SR141716A (a potent and selective antagonist of the cannabinoid receptor CB1) or NS398 [a cyclooxygenase (COX)-2 inhibitor] to determine whether any observed stimulation of PGE2 production was mediated through the CB1-receptor and/or COX-2 activity. All three cannabinoids caused a significant increase in PGE2 production in the amnion but not in the choriodecidua. However, separated fetal (chorion) explants responded to cannabinoid treatment in a similar manner to amnion, whereas maternal (decidual) explants did not. The enhanced PGE2 production caused by CP55,940 was abrogated by cotreatment with either SR141716A or NS398, illustrating that the cannabinoid action on prostaglandin production in fetal membranes is mediated by CB1 agonism and COX-2. Data from Western blotting show that cannabinoid treatment results in the upregulation of COX-2 expression. This study demonstrates a potential role for endocannabinoids in the modulation of prostaglandin production in late human pregnancy, with potentially important implications for the timing and progression of term and preterm labor and membrane rupture.

Falcarinol (Panaxynol) is a CB1 cannabinoid receptor antagonist and induces pro-allergic effects in skin

Planta Medica ◽  
2009 ◽  
Vol 75 (09) ◽  
Author(s):  
J Gertsch ◽  
M Leonti ◽  
L Casu ◽  
F Cottiglia ◽  
S Raduner ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Cannabinoid Receptor ◽  
Cb1 Cannabinoid Receptor
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