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 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.

scholarly journals Estrogens and Spermiogenesis: New Insights from Type 1 Cannabinoid Receptor Knockout Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Giovanna Cacciola ◽  
Teresa Chioccarelli ◽  
Silvia Fasano ◽  
Riccardo Pierantoni ◽  
Gilda Cobellis
Keyword(s):  
Cannabinoid Receptor ◽  
Morphological Changes ◽  
Terminal Differentiation ◽  
Environmental Chemicals ◽  
Complex Mechanism ◽  
Autocrine Factors ◽  
Estrogenic Effects ◽  
Male Gametes ◽  
Type 1 Cannabinoid Receptor

Spermatogenesis is a complex mechanism which allows the production of male gametes; it consists of mitotic, meiotic, and differentiation phases. Spermiogenesis is the terminal differentiation process during which haploid round spermatids undergo several biochemical and morphological changes, including extensive remodelling of chromatin and nuclear shape. Spermiogenesis is under control of endocrine, paracrine, and autocrine factors, like gonadotropins and testosterone. More recently, emerging pieces of evidence are suggesting that, among these factors, estrogens may have a role. To date, this is a matter of debate and concern because of the agonistic and antagonistic estrogenic effects that environmental chemicals may have on animal and human with damaging outcome on fertility. In this review, we summarize data which fuel this debate, with a particular attention to our recent results, obtained using type 1 cannabinoid receptor knockout male mice as animal model.

Astroglial type-1 cannabinoid receptor (CB1): A new player in the tripartite synapse

Neuroscience ◽  
2016 ◽  
Vol 323 ◽  
pp. 35-42 ◽  
Author(s):  
J.F. Oliveira da Cruz ◽  
L.M. Robin ◽  
F. Drago ◽  
G. Marsicano ◽  
M. Metna-Laurent
Keyword(s):  
Cannabinoid Receptor ◽  
Tripartite Synapse ◽  
Type 1 Cannabinoid Receptor

Anandamide regulates the expression of GnRH1, GnRH2, and GnRH-Rs in frog testis

2012 ◽  
Vol 303 (4) ◽  
pp. E475-E487 ◽  
Author(s):  
Rosanna Chianese ◽  
Vincenza Ciaramella ◽  
Donatella Scarpa ◽  
Silvia Fasano ◽  
Riccardo Pierantoni ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Rana Esculenta ◽  
Sexual Cycle ◽  
Human Testis ◽  
Biosynthetic Enzyme ◽  
Endogenous Production ◽  
Cb1 Antagonist ◽  
Type 1 Cannabinoid Receptor

Gonadotropin-releasing hormone (either GnRH1 or GnRH2) exerts a local activity in vertebrate testis, including human testis. Relationships between endocannabinoid (eCB) and GnRH systems in gonads have never been elucidated in any species so far. To reveal a cross-talk between eCBs and GnRH at testicular level, we characterized the expression of GnRH ( GnRH1 and GnRH2) as well as GnRH receptor ( GnRH-R1, -R2, and -R3) mRNA in the testis of the anuran amphibian Rana esculenta during the annual sexual cycle; furthermore, the corresponding transcripts were localized inside the testis by in situ hybridization. The possible endogenous production of the eCB, anandamide (AEA), was investigated in testis by analyzing the expression of its biosynthetic enzyme, Nape-pld. Incubations of testis pieces with AEA were carried out in the postreproductive period (June) and in February, when a new spermatogenetic wave takes place. In June, AEA treatment significantly decreased GnRH1 and GnRH-R2 mRNA, stimulated the transcription of GnRH2 and GnRH-R1, and did not affect GnRH-R3 expression. In February, AEA treatment upregulated GnRH2 and GnRH-R3 mRNA, downregulated GnRH-R2, and did not affect GnRH1 and GnRH-R1 expression. These effects were mediated by type 1 cannabinoid receptor ( CB1) since they were fully counteracted by SR141716A (Rimonabant), a selective CB1 antagonist. In conclusion, eCB system modulates GnRH activity in frog testis during the annual sexual cycle in a stage-dependent fashion.

scholarly journals Type 1 cannabinoid receptor modulates water deprivation-induced homeostatic responses

2015 ◽  
Vol 309 (11) ◽  
pp. R1358-R1368 ◽  
Author(s):  
Silvia G. Ruginsk ◽  
Fernanda M. V. Vechiato ◽  
Ernane T. Uchoa ◽  
Lucila L. K. Elias ◽  
Jose Antunes-Rodrigues
Keyword(s):  
Mrna Expression ◽  
Water Deprivation ◽  
Energy Homeostasis ◽  
Cannabinoid Receptor ◽  
Plasma Concentrations ◽  
Hydration Status ◽  
Potential Candidate ◽  
Mrna Levels ◽  
Type 1 Cannabinoid Receptor

The present study investigated the type 1 cannabinoid receptor (CB1R) as a potential candidate to mediate the homeostatic responses triggered by 24 h of water deprivation, which constitutes primarily a hydroelectrolytic challenge and also significantly impacts energy homeostasis. The present results demonstrated for the first time that CB1R mRNA expression is increased in the hypothalamus of water-deprived (WD) rats. Furthermore, the administration of ACEA, a CB1R selective agonist, potentiated WD-induced dipsogenic effect, whereas AM251, a CB1R antagonist, attenuated not only water but also salt intake in response to WD. In parallel with the modulation of thirst and salt appetite, we confirmed that CB1Rs are essential for the development of appropriated neuroendocrine responses. Although the administration of ACEA or AM251 did not produce any effects on WD-induced arginine vasopressin (AVP) secretion, oxytocin (OXT) plasma concentrations were significantly decreased in WD rats treated with ACEA. At the genomic level, ACEA significantly decreased AVP and OXT mRNA expression in the hypothalamus of WD rats, whereas AM251 potentiated both basal and WD-induced stimulatory effects on the transcription of AVP and OXT genes. In addition, we showed that water deprivation alone upregulated proopiomelanocortin, Agouti-related peptide, melanin-concentrating hormone, and orexin A mRNA levels in the hypothalamus, and that CB1Rs regulate main central peptidergic pathways controlling food intake, being that most of these effects were also significantly influenced by the hydration status. In conclusion, the present study demonstrated that CB1Rs participate in the homeostatic responses regulating fluid balance and energy homeostasis during water deprivation.

scholarly journals Deficiency of triad junction and contraction in mutant skeletal muscle lacking junctophilin type 1

2001 ◽  
Vol 154 (5) ◽  
pp. 1059-1068 ◽  
Author(s):  
Koichi Ito ◽  
Shinji Komazaki ◽  
Kazushige Sasamoto ◽  
Morikatsu Yoshida ◽  
Miyuki Nishi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Plasma Membrane ◽  
Physiological Role ◽  
Mutant Mice ◽  
Functional Coupling ◽  
Release Channel ◽  
Signal Conversion ◽  
Triad Junction ◽  
Triad Junctions

In skeletal muscle excitation–contraction (E–C) coupling, the depolarization signal is converted from the intracellular Ca2+ store into Ca2+ release by functional coupling between the cell surface voltage sensor and the Ca2+ release channel on the sarcoplasmic reticulum (SR). The signal conversion occurs in the junctional membrane complex known as the triad junction, where the invaginated plasma membrane called the transverse-tubule (T-tubule) is pinched from both sides by SR membranes. Previous studies have suggested that junctophilins (JPs) contribute to the formation of the junctional membrane complexes by spanning the intracellular store membrane and interacting with the plasma membrane (PM) in excitable cells. Of the three JP subtypes, both type 1 (JP-1) and type 2 (JP-2) are abundantly expressed in skeletal muscle. To examine the physiological role of JP-1 in skeletal muscle, we generated mutant mice lacking JP-1. The JP-1 knockout mice showed no milk suckling and died shortly after birth. Ultrastructural analysis demonstrated that triad junctions were reduced in number, and that the SR was often structurally abnormal in the skeletal muscles of the mutant mice. The mutant muscle developed less contractile force (evoked by low-frequency electrical stimuli) and showed abnormal sensitivities to extracellular Ca2+. Our results indicate that JP-1 contributes to the construction of triad junctions and that it is essential for the efficiency of signal conversion during E–C coupling in skeletal muscle.

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