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https://www.readbyqxmd.com/read/30546297/brain-derived-neurotrophic-factor-bdnf-role-in-cannabinoid-mediated-neurogenesis
#1
Filipa Fiel Ferreira, Filipa F Ribeiro, Rui S Rodrigues, Ana Maria Sebastião, Sara Xapelli
The adult mammalian brain can produce new neurons in a process called adult neurogenesis, which occurs mainly in the subventricular zone (SVZ) and in the hippocampal dentate gyrus (DG). Brain-derived neurotrophic factor (BDNF) signaling and cannabinoid type 1 and 2 receptors (CB1R and CB2R) have been shown to independently modulate neurogenesis, but how they may interact is unknown. We now used SVZ and DG neurosphere cultures from early (P1-3) postnatal rats to study the CB1R and CB2R crosstalk with BDNF in modulating neurogenesis...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/30522798/ventral-hippocampal-overexpression-of-cannabinoid-receptor-interacting-protein-1-cnrip1-produces-a-schizophrenia-like-phenotype-in-the-rat
#2
Stephanie M Perez, Jennifer J Donegan, Angela M Boley, David D Aguilar, Andrea Giuffrida, Daniel J Lodge
Adolescent cannabis use has been implicated as a risk factor for schizophrenia; however, it is neither necessary nor sufficient. Previous studies examining this association have focused primarily on the role of the cannabinoid receptor 1 (CB1R) with relatively little known about a key regulatory protein, the cannabinoid receptor interacting protein 1 (CNRIP1). CNRIP1 is an intracellular protein that interacts with the C-terminal tail of CB1R and regulates its intrinsic activity. Previous studies have demonstrated aberrant CNRIP1 DNA promoter methylation in post-mortem in human patients with schizophrenia, and we have recently reported decreased methylation of the CNRIP1 DNA promoter in the ventral hippocampus (vHipp) of a rodent model of schizophrenia susceptibility...
December 3, 2018: Schizophrenia Research
https://www.readbyqxmd.com/read/30498363/mir-23b-3p-and-mir-130a-5p-affect-cell-growth-migration-and-invasion-by-targeting-cb1r-via-the-wnt-%C3%AE-catenin-signaling-pathway-in-gastric-carcinoma
#3
Xiangshu Xian, Li Tang, Chengrong Wu, Liuye Huang
Background: Gastric cancer (GC) is the most common malignancy and third leading cause of cancer mortality worldwide. The identification of a sensitive biomarker as well as effective therapeutic targets for the treatment of GC is of critical importance. microRNAs play significant roles in the development of cancer and may serve as promising therapeutic targets. Methods: The mRNA and protein expression of CB1R were studied both in GC cells and tissues. GC cell lines with specific gene overexpression and knockdown vectors were constructed...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/30381869/modulation-of-gastric-acid-secretion-by-cannabinoids-in-rats
#4
Rania A A Salama, Rania M Abdelsalam, O M E Abdel-Salam, Mahmoud M Khattab, Neveen A Salem, Zakaria A El-Khyat, Fatma A Morsy, Ezz-El Din S Eldenshary
The current study aimed to evaluate the role of cannabinoid receptors in the regulation of gastric acid secretion and oxidative stress in gastric mucosa. To fulfill this aim, gastric acid secretion stimulated with histamine (5 mg/kg, subcutaneous [SC]), 2-deoxy- d-glucose (D-G) (200 mg/kg, intravenous) or -carbachol (4 μg/kg, SC) in the 4-hour pylorus-ligated rats. The CB1R agonist ( N-arachidonoyl dopamine, 1 mg/kg, SC) inhibited gastric acid secretion stimulated by D-G and carbachol but not in histamine, reduced pepsin content, and increased mucin secretion...
November 1, 2018: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/30380982/analgesic-effects-of-faah-inhibitor-in-the-insular-cortex-of-nerve-injured-rats
#5
Min Jee Kim, Motomasa Tanioka, Sun Woo Um, Seong-Karp Hong, Bae Hwan Lee
The insular cortex is an important region of brain involved in the processing of pain and emotion. Recent studies indicate that lesions in the insular cortex induce pain asymbolia and reverse neuropathic pain. Endogenous cannabinoids (endocannabinoids), which have been shown to attenuate pain, are simultaneously degraded by fatty acid amide hydrolase (FAAH) that halts the mechanisms of action. Selective inhibitor URB597 suppresses FAAH activity by conserving endocannabinoids, which reduces pain. The present study examined the analgesic effects of URB597 treatment in the insular cortex of an animal model of neuropathic pain...
January 2018: Molecular Pain
https://www.readbyqxmd.com/read/30348772/median-nerve-stimulation-induces-analgesia-via-orexin-initiated-endocannabinoid-disinhibition-in-the-periaqueductal-gray
#6
Yi-Hung Chen, Hsin-Jung Lee, Ming Tatt Lee, Ya-Ting Wu, Yen-Hsien Lee, Ling-Ling Hwang, Ming-Shiu Hung, Andreas Zimmer, Ken Mackie, Lih-Chu Chiou
Adequate pain management remains an unmet medical need. We previously revealed an opioid-independent analgesic mechanism mediated by orexin 1 receptor (OX1R)-initiated 2-arachidonoylglycerol (2-AG) signaling in the ventrolateral periaqueductal gray (vlPAG). Here, we found that low-frequency median nerve stimulation (MNS) through acupuncture needles at the PC6 (Neiguan) acupoint (MNS-PC6) induced an antinociceptive effect that engaged this mechanism. In mice, MNS-PC6 reduced acute thermal nociceptive responses and neuropathy-induced mechanical allodynia, increased the number of c-Fos-immunoreactive hypothalamic orexin neurons, and led to higher orexin A and lower GABA levels in the vlPAG...
November 6, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30339387/6-benzhydryl-4-amino-quinolin-2-ones-as-potent-cannabinoid-type-1-cb-1-receptor-inverse-agonists-and-chemical-modifications-for-peripheral-selectivity
#7
Yue-Mei Zhang, Michael N Greco, Mark J Macielag, Christopher A Teleha, Renee L DesJarlais, Yuting Tang, George Ho, Cuifen Hou, Cailin Chen, Shuyuan Zhao, Jack Kauffman, Raul Camacho, Jenson Qi, William Murray, Keith Demarest, James Leonard
A novel series of 6-benzhydryl-4-amino-quinolin-2-ones was discovered as cannabinoid type 1 receptor (CB1 R) inverse agonists based on the high-throughput screening hit, compound 1a. Structure-activity relationships were studied to improve in vitro/in vivo pharmacology and restrict distribution to the peripheral circulation. We adopted several strategies such as increasing topological polar surface area, incorporating discrete polyethylene glycol side chains, and targeting P-glycoprotein (P-gp) to minimize access to the brain...
October 31, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/30319418/atypical-pharmacodynamic-properties-and-metabolic-profile-of-the-abused-synthetic-cannabinoid-ab-pinaca-potential-contribution-to-pronounced-adverse-effects-relative-to-%C3%AE-9-thc
#8
Rachel D Hutchison, Benjamin M Ford, Lirit N Franks, Catheryn D Wilson, Azure L Yarbrough, Ryoichi Fujiwara, Mark K Su, Denise Fernandez, Laura P James, Jeffery H Moran, Amy L Patton, William E Fantegrossi, Anna Radominska-Pandya, Paul L Prather
Recreational use of marijuana is associated with few adverse effects, but abuse of synthetic cannabinoids (SCBs) can result in anxiety, psychosis, chest pain, seizures and death. To potentially explain higher toxicity associated with SCB use, we hypothesized that AB-PINACA, a common second generation SCB, exhibits atypical pharmacodynamic properties at CB1 cannabinoid receptors (CB1Rs) and/or a distinct metabolic profile when compared to Δ9 -tetrahydrocannabinol (Δ9 -THC), the principal psychoactive cannabinoid present in marijuana...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/30317131/endocannabinoid-mediated-modulation-of-gq-protein-coupled-receptor-mediates-vascular-hyporeactivity-to-nor-adrenaline-during-polymicrobial-sepsis
#9
Preeti Singh, Pranshu Sharma, Udayraj P Nakade, Abhishek Sharma, Manju Gari, Soumen Choudhury, Amit Shukla, Satish Kumar Garg
BACKGROUND: Endocannabinoids level are reported to increase in sepsis, however, the role of vascular cannabinoid receptor-1 (CB1R) in sepsis-induced vascular hyporeactivity is yet to be unravelled. METHODS: Polymicrobial sepsis was induced by caecal ligation and puncture in mice. Isometric tension in isolated aortic rings during early (6 h) and late (20 h) phases of sepsis was recorded and expression of mRNA of monoacylglycerol lipase (MAGL) and cannabinoid receptor-1 (CB1R) was investigated...
July 19, 2018: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/30300803/assessment-of-rimonabant-like-adverse-effects-of-purported-cb1r-neutral-antagonist-cb2r-agonist-aminoalkylindole-derivatives-in-mice
#10
Sherrica Tai, Tamara Vasiljevik, Alexander M Sherwood, Sarah Eddington, Catheryn D Wilson, Thomas E Prisinzano, William E Fantegrossi
BACKGROUND: Cannabinoids may be useful in the treatment of CNS disorders including drug abuse and addiction, where both CB1R antagonists / inverse agonists and CB2R agonists have shown preclinical efficacy. TV-5-249 and TV-6-41, two novel aminoalkylindoles with dual action as neutral CB1R antagonists and CB2R agonists, previously attenuated abuse-related effects of ethanol in mice. PURPOSE: To further characterize these drugs, TV-5-249 and TV-6-41 were compared with the CB1R antagonist / inverse agonist rimonabant in assays relevant to adverse effects and cannabinoid withdrawal...
November 1, 2018: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/30296558/sex-difference-in-brain-cb1-receptor-availability-in-man
#11
Heikki Laurikainen, Lauri Tuominen, Maria Tikka, Harri Merisaari, Reetta-Liina Armio, Elina Sormunen, Faith Borgan, Mattia Veronese, Oliver Howes, Merja Haaparanta-Solin, Olof Solin, Jarmo Hietala
The endocannabinoid system (ECS) has a widespread neuromodulatory function in the central nervous system and is involved in important aspects of brain function including brain development, cortical rhythms, plasticity, reward, and stress sensitivity. Many of these effects are mediated via the cannabinoid CB1 receptor (CB1R) subtype. Animal studies convincingly show an interaction between the ECS and sex hormones, as well as a sex difference of higher brain CB1R in males. Human in vivo studies of sex difference have yielded discrepant findings...
January 1, 2019: NeuroImage
https://www.readbyqxmd.com/read/30273593/repeated-cannabidiol-treatment-reduces-cocaine-intake-and-modulates-neural-proliferation-and-cb1r-expression-in-the-mouse-hippocampus
#12
Miguel Ángel Luján, Adriana Castro-Zavala, Laia Alegre-Zurano, Olga Valverde
Cannabinoid derivatives have shown promising results for treating neuropsychiatric disorders, including drug addiction. Recent studies on the therapeutic effects of Cannabidiol (CBD) on drug abuse showed mixed results, especially with psychostimulant substances such as cocaine. To determine whether CBD can attenuate cocaine reinforcement, we assessed behavioural responses induced by cocaine in mice, using the behavioural sensitization, conditioned place preference and intravenous self-administration paradigms...
December 2018: Neuropharmacology
https://www.readbyqxmd.com/read/30257184/%C3%AE-lactams-modulate-astroglial-glutamate-transporters-and-attenuate-dependence-to-cp-55-940-a-cb1-receptor-agonist-in-rat-model
#13
Alqassem Y Hakami, Fahad S Alshehri, Youssef Sari
Studies on cannabinoids have reported contradictory findings, showing both aversion and rewarding outcomes in conditioned place preference (CPP). Various possibilities have been suggested to explain the aversive properties of cannabinoids, including the pharmacokinetics profile and dose selection. In this study, we have established a CPP method to investigate the effects of modulating astroglial glutamate transporters in cannabinoid dependence using a cannabinoid receptor 1 (CB1R) agonist, CP 55,940 (CP). Previous reports using CPP paradigm demonstrated the involvement of glutamatergic system in seeking behavior of several drugs of abuse such as cocaine, heroin and nicotine...
September 23, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/30246417/design-synthesis-and-sar-studies-of-heteroarylpyrimidines-and-heteroaryltriazines-as-cb-2-r-ligands
#14
Hai-Yan Qian, Zhi-Long Wang, Li-Li Chen, You-Lu Pan, Xiao-Yu Xie, Xin Xie, Jian-Zhong Chen
Herein we describe the design and synthesis of a new series of heteroarylpyrimidine/heteroaryltriazine derivatives on the basis of quinazoline-2,4(1H,3H)-diones as CB2 R-selective ligands using a bioisosterism strategy. An acetamide group was explored to displace the enamine linker of the lead compound for the purpose of stereoisomerism elimination and hydrophilicity increase. As a result, some of the synthesized compounds showed high bioactivity and selectivity for CB2 R in calcium mobilization assays, and four displayed CB2 R agonist activity, with EC50 values below 30 nm...
September 24, 2018: ChemMedChem
https://www.readbyqxmd.com/read/30217553/cb1-receptors-in-the-paraventricular-nucleus-of-the-hypothalamus-modulate-the-release-of-5-ht-and-gaba-to-stimulate-food-intake-in-rats
#15
Ana María Cruz-Martínez, Juan Gabriel Tejas-Juárez, Juan Manuel Mancilla-Díaz, Benjamín Florán-Garduño, Verónica Elsa López-Alonso, Rodrigo Erick Escartín-Pérez
Endocannabinoids and their receptors not only contribute to the control of natural processes of appetite regulation and energy balance but also have an important role in the pathogenesis of obesity. CB1 receptors (CB1R) are expressed in several hypothalamic nuclei, including the paraventricular nucleus (PVN), where induce potent orexigenic responses. Activation of CB1R in the PVN induces hyperphagia by modulating directly or indirectly orexigenic and anorexigenic signals; however, interaction among these mediators has not been clearly defined...
September 11, 2018: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/30216767/glucocorticoid-interactions-with-the-dorsal-striatal-endocannabinoid-system-in-regulating-inhibitory-avoidance-memory
#16
Cristina Siller-Pérez, Antonio Fuentes-Ibañez, Erika L Sotelo-Barrera, Norma Serafín, Roberto A Prado-Alcalá, Patrizia Campolongo, Benno Roozendaal, Gina L Quirarte
The endocannabinoid (eCB) system is highly stress sensitive and known to modulate memory formation of emotionally arousing experiences across different corticolimbic structures. eCB signaling within these circuits is also essentially involved in regulating non-genomically mediated glucocorticoid hormone effects on memory. It has long been thought that the dorsal striatum, which plays a major role in procedural memory and habit formation, is considerably less impacted by stressful experiences; however, recent findings indicate that stress and glucocorticoids also affect striatal-dependent memory processes...
August 30, 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/30184259/reversal-of-albuminuria-by-combined-am6545-and-perindopril-therapy-in-experimental-diabetic-nephropathy
#17
F Barutta, S Bellini, R Mastrocola, R Gambino, F Piscitelli, V di Marzo, B Corbetta, V K Vemuri, A Makriyannis, L Annaratone, G Bruno, G Gruden
BACKGROUND AND PURPOSE: The endocannabinoid (EC) system has been implicated in the pathogenesis of diabetic nephropathy (DN). We investigated the effects of peripheral blockade of the cannabinoid CB1 receptor as an add-on treatment to ACE-inhibition in type 1 diabetic mice (DM) with established albuminuria. EXPERIMENTAL APPROACH: Renal functional parameters (albumin excretion rate, creatinine clearance), tubular injury, renal structure, both EC and CB receptor levels and markers of podocyte dysfunction, fibrosis and inflammation were studied in streptozotocin-induced DM treated for 14 weeks with vehicle, the ACE-inhibitor perindopril (2 mg·kg-1 ·day-1 ), peripherally-restricted CB1 receptor antagonist AM6545 (10 mg·kg-1 ·day-1 ) or both...
December 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/30165669/a-cannabinoid-receptor-type-1-cb1r-agonist-enhances-the-developmental-neurotoxicity-of-acetaminophen-paracetamol
#18
Gaëtan Philippot, Stefan Hallgren, Torsten Gordh, Anders Fredriksson, Robert Fredriksson, Henrik Viberg
Acetaminophen (AAP; also known as paracetamol) is the most used and only recommended analgesic and antipyretic among pregnant women and young children. However, recent findings in both humans and rodents suggest a link between developmental exposure to AAP and adverse neurobehavioral effects later in life. We hypothesized that the cannabinoid receptor type 1 (CB1R) may be involved in the developmental neurotoxicity of AAP, owing to its interaction with the endocannabinoid system. Here we test if CB1R agonist WIN 55 212-2 (WIN) and AAP can interact when exposure occurs during a neurodevelopmental stage known for increased growth rate and for its vulnerability to AAP exposure...
November 1, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30152105/dietary-galacto-oligosaccharides-and-resistant-starch-protect-against-altered-cb1-and-5-ht1a-and-2a-receptor-densities-in-rat-brain-implications-for-preventing-cognitive-and-appetite-dysfunction-during-a-high-fat-diet
#19
Yinghua Yu, Craig Patch, Katrina Weston-Green, Yuan Zhou, Kuiyang Zheng, Xu-Feng Huang
SCOPE: A high-fat, but low-fiber, diet is associated with obesity and cognitive dysfunction, while dietary fiber supplementation can improve cognition. METHODS AND RESULTS: This study examines whether dietary fibers, galacto-oligosaccharides (GOS) and resistant starch (RS), could prevent high-fat (HF)-diet-induced alterations in neurotransmitter receptor densities in brain regions associated with cognition and appetite. Rats are fed a HF diet, HF diet with GOS, HF diet with RS, or a low-fat (LF, control) diet for 4 weeks...
August 27, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/30151725/astrocytic-mechanisms-involving-kynurenic-acid-control-%C3%AE-9-tetrahydrocannabinol-induced-increases-in-glutamate-release-in-brain-reward-processing-areas
#20
Maria E Secci, Paola Mascia, Claudia Sagheddu, Sarah Beggiato, Miriam Melis, Andrea C Borelli, Maria C Tomasini, Leigh V Panlilio, Charles W Schindler, Gianluigi Tanda, Sergi Ferré, Charles W Bradberry, Luca Ferraro, Marco Pistis, Steven R Goldberg, Robert Schwarcz, Zuzana Justinova
The reinforcing effects of Δ9 -tetrahydrocannabinol (THC) in rats and monkeys, and the reinforcement-related dopamine-releasing effects of THC in rats, can be attenuated by increasing endogenous levels of kynurenic acid (KYNA) through systemic administration of the kynurenine 3-monooxygenase inhibitor, Ro 61-8048. KYNA is a negative allosteric modulator of α7 nicotinic acetylcholine receptors (α7nAChRs) and is synthesized and released by astroglia, which express functional α7nAChRs and cannabinoid CB1 receptors (CB1Rs)...
August 27, 2018: Molecular Neurobiology
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