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.

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.

Synthesis and Characterization of NESS 0327: A Novel Putative Antagonist of the CB1 Cannabinoid Receptor

2003 ◽  
Vol 306 (1) ◽  
pp. 363-370 ◽  
Author(s):  
Stefania Ruiu ◽  
Gèrard A. Pinna ◽  
Giorgio Marchese ◽  
Jean-Mario Mussinu ◽  
Pierluigi Saba ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Synthesis And Characterization ◽  
Cb1 Cannabinoid Receptor

Characterization of CB1 cannabinoid receptor immunoreactivity in postmortem human brain homogenates

Neuroscience ◽  
2006 ◽  
Vol 140 (2) ◽  
pp. 635-643 ◽  
Author(s):  
M. López De Jesús ◽  
J. Sallés ◽  
J.J. Meana ◽  
L.F. Callado
Keyword(s):  
Human Brain ◽  
Cannabinoid Receptor ◽  
Postmortem Human Brain ◽  
Cb1 Cannabinoid Receptor

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.

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

Characterization of Ischemic Stroke in CT Images using Image Processing

2017 ◽  
Vol 7 (9) ◽  
pp. 18
Author(s):  
Amal Alzain ◽  
Suhaib Alameen ◽  
Rani Elmaki ◽  
Mohamed E. M. Gar-Elnabi
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Classification Accuracy ◽  
Ct Images ◽  
Gray Level ◽  
Level Variation ◽  
Interactive Data ◽  
The Brain ◽  
Brain Tissues

This study concern to characterize the brain tissues to ischemic stroke, gray matter, white matter and CSF using texture analysisto extract classification features from CT images. The First Order Statistic techniques included sevenfeatures. To find the gray level variation in CT images it complements the FOS features extracted from CT images withgray level in pixels and estimate the variation of thesubpatterns. analyzing the image with Interactive Data Language IDL software to measure the grey level of images. The results show that the Gray Level variation and   features give classification accuracy of ischemic stroke 97.6%, gray matter95.2%, white matter 97.3% and the CSF classification accuracy 98.0%. The overall classification accuracy of brain tissues 97.0%.These relationships are stored in a Texture Dictionary that can be later used to automatically annotate new CT images with the appropriate brain tissues names.

Sign in / Sign up

Export Citation Format

Share Document