scholarly journals Cannabinoid receptors distribution in mouse cortical plasma membrane compartments

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Hajar Miranzadeh Mahabadi ◽  
Haseeb Bhatti ◽  
Robert B. Laprairie ◽  
Changiz Taghibiglou
Keyword(s):  
Plasma Membrane ◽  
Lipid Raft ◽  
Cannabinoid Receptors ◽  
Gradient Centrifugation ◽  
Brain Regions ◽  
Cb1 Receptor ◽  
The Body ◽  
Cb2 Receptor ◽  
Cortical Tissue ◽  
Ionic Detergent

AbstractThe type 1 and type 2 cannabinoid receptors (CB1 and CB2 receptors) are class A G protein-coupled receptors (GPCRs) that are activated by endogenous lipids called endocannabinoids to modulate neuronal excitability and synaptic transmission in neurons throughout the central nervous system (CNS), and inflammatory processes throughout the body. CB1 receptor is one of the most abundant GPCRs in the CNS and is involved in many physiological and pathophysiological processes, including mood, appetite, and nociception. CB2 receptor is primarily found on immunomodulatory cells of both the CNS and the peripheral immune system. In this study, we isolated lipid raft and non-lipid raft fractions of plasma membrane (PM) from mouse cortical tissue by using cold non-ionic detergent and sucrose gradient centrifugation to study the localization of CB1 receptor and CB2 receptor. Lipid raft and non-lipid raft fractions were confirmed by flotillin-1, caveolin-1 and transferrin receptor as their protein biomarkers. Both CB1 receptor and CB2 receptor were found in non-raft compartments that is inconsistent with previous findings in cultured cell lines. This study demonstrates compartmentalization of both CB1 receptor and CB2 receptor in cortical tissue and warrants further investigation of CB1 receptor and CB2 receptor compartmental distribution in various brain regions and cell types.

Role of cannabinoid receptors in alcoholic hepatic injury: steatosis and fibrogenesis are increased in CB2 receptor-deficient mice and decreased in CB1 receptor knockouts

2011 ◽  
Vol 31 (6) ◽  
pp. 860-870 ◽  
Author(s):  
Jonel Trebicka ◽  
Ildiko Racz ◽  
Sören V. Siegmund ◽  
Erlind Cara ◽  
Michaela Granzow ◽  
...  
Keyword(s):  
Cannabinoid Receptors ◽  
Hepatic Injury ◽  
Cb1 Receptor ◽  
Cb2 Receptor ◽  
Deficient Mice

scholarly journals Role of Cannabinoid Receptors in Psychological Disorder

2020 ◽  
Vol 3 (4) ◽  
pp. 199-208
Author(s):  
Ambika Nand Jha ◽  
Dhaval M Patel
Keyword(s):  
Cannabinoid Receptors ◽  
Biological Effects ◽  
Endocannabinoid System ◽  
Brain Regions ◽  
The Body ◽  
Psychological Disorder ◽  
Physiological Processes ◽  
Neurochemical Changes ◽  
G Protein Coupled

Cannabinoid receptors, located throughout the body, are part of the endocannabinoid system. Cannabinoid CB1 and CB2 receptors are G protein-coupled receptors present from the early stages of gestation, which is involved in various physiological processes, including appetite, pain-sensation, mood, and memory. Due to the lipophilic nature of cannabinoids, it was initially thought that these compounds exert several biological effects by disrupting the cell membrane nonspecifically. Recent biochemical and behavioral findings have demonstrated that blockade of CB1 receptors engenders antidepressant-like neurochemical changes (increases in extracellular levels of monoamines in cortical but not subcortical brain regions) and behavioral effects consistent with antidepressant/antistress activity. We aim to define various roles of cannabinoid receptors in modulating signaling pathways and association with several pathophysiological conditions.

scholarly journals Subsynaptic Distribution, Lipid Raft Targeting and G Protein-Dependent Signalling of the Type 1 Cannabinoid Receptor in Synaptosomes from the Mouse Hippocampus and Frontal Cortex

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6897
Author(s):  
Miquel Saumell-Esnaola ◽  
Sergio Barrondo ◽  
Gontzal García del Caño ◽  
María Aranzazu Goicolea ◽  
Joan Sallés ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Frontal Cortex ◽  
Lipid Raft ◽  
Cannabinoid Receptor ◽  
Cb1 Receptor ◽  
Gabaergic Neurons ◽  
Functional Coupling ◽  
Cell Type ◽  
Type 1 Cannabinoid Receptor

Numerous studies have investigated the roles of the type 1 cannabinoid receptor (CB1) in glutamatergic and GABAergic neurons. Here, we used the cell-type-specific CB1 rescue model in mice to gain insight into the organizational principles of plasma membrane targeting and Gαi/o protein signalling of the CB1 receptor at excitatory and inhibitory terminals of the frontal cortex and hippocampus. By applying biochemical fractionation techniques and Western blot analyses to synaptosomal membranes, we explored the subsynaptic distribution (pre-, post-, and extra-synaptic) and CB1 receptor compartmentalization into lipid and non-lipid raft plasma membrane microdomains and the signalling properties. These data infer that the plasma membrane partitioning of the CB1 receptor and its functional coupling to Gαi/o proteins are not biased towards the cell type of CB1 receptor rescue. The extent of the canonical Gαi/o protein-dependent CB1 receptor signalling correlated with the abundance of CB1 receptor in the respective cell type (glutamatergic versus GABAergic neurons) both in frontal cortical and hippocampal synaptosomes. In summary, our results provide an updated view of the functional coupling of the CB1 receptor to Gαi/o proteins at excitatory and inhibitory terminals and substantiate the utility of the CB1 rescue model in studying endocannabinoid physiology at the subcellular level.

scholarly journals The Emerging Role of the Endocannabinoid System in Endocrine Regulation and Energy Balance

2005 ◽  
Vol 27 (1) ◽  
pp. 73-100 ◽  
Author(s):  
Uberto Pagotto ◽  
Giovanni Marsicano ◽  
Daniela Cota ◽  
Beat Lutz ◽  
Renato Pasquali
Keyword(s):  
Energy Balance ◽  
Food Intake ◽  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
Cb1 Receptor ◽  
Endocrine Regulation ◽  
Cb2 Receptor ◽  
Peripheral Tissues ◽  
The Brain

During the last few years, the endocannabinoid system has emerged as a highly relevant topic in the scientific community. Many different regulatory actions have been attributed to endocannabinoids, and their involvement in several pathophysiological conditions is under intense scrutiny. Cannabinoid receptors, named CB1 receptor and CB2 receptor, first discovered as the molecular targets of the psychotropic component of the plant Cannabis sativa, participate in the physiological modulation of many central and peripheral functions. CB2 receptor is mainly expressed in immune cells, whereas CB1 receptor is the most abundant G protein-coupled receptor expressed in the brain. CB1 receptor is expressed in the hypothalamus and the pituitary gland, and its activation is known to modulate all the endocrine hypothalamic-peripheral endocrine axes. An increasing amount of data highlights the role of the system in the stress response by influencing the hypothalamic-pituitary-adrenal axis and in the control of reproduction by modifying gonadotropin release, fertility, and sexual behavior. The ability of the endocannabinoid system to control appetite, food intake, and energy balance has recently received great attention, particularly in the light of the different modes of action underlying these functions. The endocannabinoid system modulates rewarding properties of food by acting at specific mesolimbic areas in the brain. In the hypothalamus, CB1 receptor and endocannabinoids are integrated components of the networks controlling appetite and food intake. Interestingly, the endocannabinoid system was recently shown to control metabolic functions by acting on peripheral tissues, such as adipocytes, hepatocytes, the gastrointestinal tract, and, possibly, skeletal muscle. The relevance of the system is further strenghtened by the notion that drugs interfering with the activity of the endocannabinoid system are considered as promising candidates for the treatment of various diseases, including obesity.

An Ultrastructural Study of Pericytes

1968 ◽  
Vol 26 ◽  
pp. 66-67
Author(s):  
T. M. Murad ◽  
E. von Haam
Keyword(s):  
Plasma Membrane ◽  
Endothelial Cell ◽  
Basement Membrane ◽  
Blood Vessel ◽  
Vascular Endothelial Cells ◽  
Myoepithelial Cells ◽  
Capillary Blood ◽  
The Body ◽  
Capillary Blood Vessel ◽  
Outer Plasma Membrane

Pericytes are vascular satellites present around capillary blood vessels and small venules. They have been observed in almost every tissue of the body and are thought to be related to vascular smooth muscle cells. Morphologically pericytes have great similarity to vascular endothelial cells and also slightly resemble myoepithelial cells.The present study describes the ultrastructural morphology of pericytes in normal breast tissue and in benign tumor of the breast. The study showed that pericytes are ovoid or elongated cells separated from the endothelial cell of the capillary blood vessel by the basement membrane of endothelial cell. The nuclei of pericytes are often very distinctive. Although some are round, oval, or elongated, others show marked irregularity and infolding of the nuclear membrane. The cytoplasm shows mono-or bipolar extension in which the cytoplasmic organelles are located (Fig. 1). These cytoplasmic extensions embrace the capillary blood vessel incompletely. The plasma membrane exhibits multiple areas of focal condensation called hemidesmosomes (Fig. 2, arrow). A variable number of pinocytotic vesicles are frequently seen lining the outer plasma membrane. Normally pericytes are surrounded by a basement membrane which is found more consistently on the outer plasma membrane separating the pericytes from the stromal connective tissue.

scholarly journals Epigenetic Regulation of Cannabinoid-Mediated Attenuation of Inflammation and Its Impact on the Use of Cannabinoids to Treat Autoimmune Diseases

2021 ◽  
Vol 22 (14) ◽  
pp. 7302
Author(s):  
Bryan Latrell Holloman ◽  
Mitzi Nagarkatti ◽  
Prakash Nagarkatti
Keyword(s):  
Autoimmune Diseases ◽  
Chronic Inflammation ◽  
Cannabinoid Receptors ◽  
T Regulatory Cells ◽  
Neurological Diseases ◽  
Suppressor Cells ◽  
The Body ◽  
New Class ◽  
Wide Range ◽  
Clinical Disorders

Chronic inflammation is considered to be a silent killer because it is the underlying cause of a wide range of clinical disorders, from cardiovascular to neurological diseases, and from cancer to obesity. In addition, there are over 80 different types of debilitating autoimmune diseases for which there are no cure. Currently, the drugs that are available to suppress chronic inflammation are either ineffective or overtly suppress the inflammation, thereby causing increased susceptibility to infections and cancer. Thus, the development of a new class of drugs that can suppress chronic inflammation is imperative. Cannabinoids are a group of compounds produced in the body (endocannabinoids) or found in cannabis (phytocannabinoids) that act through cannabinoid receptors and various other receptors expressed widely in the brain and immune system. In the last decade, cannabinoids have been well established experimentally to mediate anti-inflammatory properties. Research has shown that they suppress inflammation through multiple pathways, including apoptosis and inducing immunosuppressive T regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Interestingly, cannabinoids also mediate epigenetic alterations in genes that regulate inflammation. In the current review, we highlight how the epigenetic modulations caused by cannabinoids lead to the suppression of inflammation and help identify novel pathways that can be used to target autoimmune diseases.

scholarly journals RalA and RalB Proteins Are Ubiquitinated GTPases, and Ubiquitinated RalA Increases Lipid Raft Exposure at the Plasma Membrane

2012 ◽  
Vol 287 (35) ◽  
pp. 29397-29405 ◽  
Author(s):  
Vincent Neyraud ◽  
Vasily N. Aushev ◽  
Anastassia Hatzoglou ◽  
Brigitte Meunier ◽  
Ilaria Cascone ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Lipid Raft

scholarly journals Lipid raft–dependent plasma membrane repair interferes with the activation of B lymphocytes

2015 ◽  
Vol 211 (6) ◽  
pp. 1193-1205 ◽  
Author(s):  
Heather Miller ◽  
Thiago Castro-Gomes ◽  
Matthias Corrotte ◽  
Christina Tam ◽  
Timothy K. Maugel ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
B Cell ◽  
B Lymphocytes ◽  
Lipid Rafts ◽  
Lipid Raft ◽  
Cell Activation ◽  
Dependent Manner ◽  
B Cell Activation ◽  
Membrane Repair ◽  
Membrane Injury

Cells rapidly repair plasma membrane (PM) damage by a process requiring Ca2+-dependent lysosome exocytosis. Acid sphingomyelinase (ASM) released from lysosomes induces endocytosis of injured membrane through caveolae, membrane invaginations from lipid rafts. How B lymphocytes, lacking any known form of caveolin, repair membrane injury is unknown. Here we show that B lymphocytes repair PM wounds in a Ca2+-dependent manner. Wounding induces lysosome exocytosis and endocytosis of dextran and the raft-binding cholera toxin subunit B (CTB). Resealing is reduced by ASM inhibitors and ASM deficiency and enhanced or restored by extracellular exposure to sphingomyelinase. B cell activation via B cell receptors (BCRs), a process requiring lipid rafts, interferes with PM repair. Conversely, wounding inhibits BCR signaling and internalization by disrupting BCR–lipid raft coclustering and by inducing the endocytosis of raft-bound CTB separately from BCR into tubular invaginations. Thus, PM repair and B cell activation interfere with one another because of competition for lipid rafts, revealing how frequent membrane injury and repair can impair B lymphocyte–mediated immune responses.

Actomyosin motor in the merozoite of the malaria parasite, Plasmodium falciparum: implications for red cell invasion

1998 ◽  
Vol 111 (13) ◽  
pp. 1831-1839 ◽  
Author(s):  
J.C. Pinder ◽  
R.E. Fowler ◽  
A.R. Dluzewski ◽  
L.H. Bannister ◽  
F.M. Lavin ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasma Membrane ◽  
Toxoplasma Gondii ◽  
Malaria Parasite ◽  
Cellular Protein ◽  
Red Cell ◽  
Parasite Protein ◽  
Ionic Detergent ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum

The genome of the malaria parasite, Plasmodium falciparum, contains a myosin gene sequence, which bears a close homology to one of the myosin genes found in another apicomplexan parasite, Toxoplasma gondii. A polyclonal antibody was generated against an expressed polypeptide of molecular mass 27,000, based on part of the deduced sequence of this myosin. The antibody reacted with the cognate antigen and with a component of the total parasite protein on immunoblots, but not with vertebrate striated or smooth muscle myosins. It did, however, recognise two components in the cellular protein of Toxoplasma gondii. The antibody was used to investigate stage-specificity of expression of the myosin (here designated Pf-myo1) in P. falciparum. The results showed that the protein is synthesised in mature schizonts and is present in merozoites, but vanishes after the parasite enters the red cell. Pf-myo1 was found to be largely, though not entirely, associated with the particulate parasite cell fraction and is thus presumably mainly membrane bound. It was not solubilised by media that would be expected to dissociate actomyosin or myosin filaments, or by non-ionic detergent. Immunofluorescence revealed that in the merozoite and mature schizont Pf-myo1 is predominantly located around the periphery of the cell. Immuno-gold electron microscopy also showed the presence of the myosin around almost the entire parasite periphery, and especially in the region surrounding the apical prominence. Labelling was concentrated under the plasma membrane but was not seen in the apical prominence itself. This suggests that Pf-myo1 is associated with the plasma membrane or with the outer membrane of the subplasmalemmal cisterna, which forms a lining to the plasma membrane, with a gap at the apical prominence. The results lead to a conjectural model of the invasion mechanism.

scholarly journals Immunocytochemical localization and biochemical characterization of a novel plasma membrane-associated, neutral pH optimum α-l-fucosidase from rat testis and epididymal spermatozoa

1996 ◽  
Vol 318 (3) ◽  
pp. 821-831 ◽  
Author(s):  
Manuel AVILÉS ◽  
Irene ABASCAL ◽  
José Angel MARTÍNEZ-MENÁRGUEZ ◽  
María Teresa CASTELLS ◽  
Sheri R. SKALABAN ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Plasma Membranes ◽  
Biochemical Characterization ◽  
Gradient Centrifugation ◽  
Light And Electron Microscopy ◽  
Enzymic Activity ◽  
Epididymal Sperm ◽  
Sucrose Density Gradient Centrifugation ◽  
Ph Optimum ◽  
Neutral Ph

1. Immunocytochemical and biochemical techniques have been used to localize and characterize a novel plasma membrane-associated, neutral-pH-optimum α-l-fucosidase from rat spermatozoa. Light and electron microscopy specifically localized the fucosidase on the plasma membrane of the convex region of the principal segment of testicular and cauda epididymal sperm heads. Immunoreactivity for α-l-fucosidase was also detected in the Golgi apparatus of spermatocytes and spermatids but no immunoreactivity was observed in the acrosome. 2. Fractionation of epididymal sperm homogenates indicated that over 90% of the α-l-fucosidase activity was associated with the 48000 g pellet. This pellet-associated activity could be solubilized with 0.5 M NaCl but not with 0.5% Triton X-100, suggesting that fucosidase is peripherally associated with membranes. Sucrose-density-gradient centrifugation of sperm homogenates indicated that fucosidase was enriched in the plasma membrane-enriched fraction. Analysis of α-l-fucosidase on intact epididymal sperm indicated that the enzyme was active, displayed linear kinetics and had a pH–activity curve (with an optimum near 7) which was comparable to that of fucosidase from epididymal sperm extracts. These results further suggest that fucosidase is associated with plasma membranes, and that its active site is accessible to fucoconjugates. Evidence that most of the fucosidase is associated with the exterior of the plasma membrane came from studies in which intact sperm had fucosidase activity comparable to that of sperm sonicates, and from studies in which approx. 90% of the fucosidase activity on intact sperm could be released from the sperm by gentle shaking with 0.5 M NaCl. Isoelectric focusing indicated that the NaCl-solubilized epididymal sperm fucosidase appears to have one major and one minor isoform with pIs near 7.2 and 5.2, respectively. SDS/PAGE and Western blotting indicated that the NaCl-solubilized extract of epididymal sperm contains two protein bands of 54 and 50 kDa which were highly immunoreactive with the IgG fraction of anti-fucosidase antibodies. Although the function of the novel sperm fucosidase is not known, its specific localization to the plasma membrane of the region of the rat sperm head involved in sperm–egg binding and its high enzymic activity at neutral pH on intact sperm suggest that this enzyme may have a role in sperm–egg interactions.

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