Search results for "Receptor type"
showing 10 items of 121 documents
CB1 Cannabinoid Receptors and On-Demand Defense Against Excitotoxicity
2003
Abnormally high spiking activity can damage neurons. Signaling systems to protect neurons from the consequences of abnormal discharge activity have been postulated. We generated conditional mutant mice that lack expression of the cannabinoid receptor type 1 in principal forebrain neurons but not in adjacent inhibitory interneurons. In mutant mice,the excitotoxin kainic acid (KA) induced excessive seizures in vivo. The threshold to KA-induced neuronal excitation in vitro was severely reduced in hippocampal pyramidal neurons of mutants. KA administration rapidly raised hippocampal levels of anandamide and induced protective mechanisms in wild-type principal hippocampal neurons. These protecti…
A runner’s high depends on cannabinoid receptors in mice
2015
Exercise is rewarding, and long-distance runners have described a runner's high as a sudden pleasant feeling of euphoria, anxiolysis, sedation, and analgesia. A popular belief has been that endogenous endorphins mediate these beneficial effects. However, running exercise increases blood levels of both β-endorphin (an opioid) and anandamide (an endocannabinoid). Using a combination of pharmacologic, molecular genetic, and behavioral studies in mice, we demonstrate that cannabinoid receptors mediate acute anxiolysis and analgesia after running. We show that anxiolysis depends on intact cannabinoid receptor 1 (CB1) receptors on forebrain GABAergic neurons and pain reduction on activation of pe…
L-NAME induces direct arteriolar leukocyte adhesion, which is mainly mediated by angiotensin-II.
2005
Acute inhibition (1 h) of nitric oxide synthase (NOS) with L-NAME causes leukocyte recruitment in the rat mesenteric postcapillary venules that is angiotensin-II (Ang-II) dependent. Since 4-h exposure to Ang-II provokes arteriolar leukocyte adhesion, this study was designed to investigate whether subacute (4-h) NOS inhibition also causes this effect.Rats were intraperitoneally injected with saline, L-NAME, or 1H-[1,2,4]-oxidazolol-[4,3-a]-quinoxalin-1-one (ODQ). Leukocyte accumulation in the mesenteric microcirculation was examined 4 h later via intravital microscopy. Some groups were pretreated with losartan, an AT(1) Ang-II receptor antagonist.At 4-h, L-NAME caused a significant increase …
Loss of striatal type 1 cannabinoid receptors is a key pathogenic factor in Huntington's disease.
2010
Endocannabinoids act as neuromodulatory and neuroprotective cues by engaging type 1 cannabinoid receptors. These receptors are highly abundant in the basal ganglia and play a pivotal role in the control of motor behaviour. An early downregulation of type 1 cannabinoid receptors has been documented in the basal ganglia of patients with Huntington's disease and animal models. However, the pathophysiological impact of this loss of receptors in Huntington's disease is as yet unknown. Here, we generated a double-mutant mouse model that expresses human mutant huntingtin exon 1 in a type 1 cannabinoid receptor-null background, and found that receptor deletion aggravates the symptoms, neuropatholog…
Understanding Cannabinoid Psychoactivity with Mouse Genetic Models
2007
Marijuana and its main psychotropic ingredient Δ9-tetrahydrocannabinol (THC) exert a plethora of psychoactive effects through the activation of the neuronal cannabinoid receptor type 1 (CB1), which is expressed by different neuronal subpopulations in the central nervous system. The exact neuroanatomical substrates underlying each effect of THC are, however, not known. We tested locomotor, hypothermic, analgesic, and cataleptic effects of THC in conditional knockout mouse lines, which lack the expression of CB1 in different neuronal subpopulations, including principal brain neurons, GABAergic neurons (those that release γ aminobutyric acid), cortical glutamatergic neurons, and neurons expres…
Nitroglycerin-induced endothelial dysfunction and tolerance involve adverse phosphorylation and S-glutathionylation of endothelial nitric oxide synth…
2011
Continuous administration of nitroglycerin (GTN) causes tolerance and endothelial dysfunction by inducing reactive oxygen species (ROS) production from various enzymatic sources, such as mitochondria, NADPH oxidase, and an uncoupled endothelial nitric oxide synthase (eNOS). In the present study, we tested the effects of type 1 angiotensin (AT(1))-receptor blockade with telmisartan on GTN-induced endothelial dysfunction in particular on eNOS phosphorylation and S-glutathionylation sites and the eNOS cofactor synthesizing enzyme GTP-cyclohydrolase I.Wistar rats were treated with telmisartan (2.7 or 8 mg/kg per day PO for 10 days) and with GTN (50 mg/kg per day SC for 3 days). Aortic eNOS phos…
Double Negative (IgG+IgD-CD27-) B Cells are Increased in a Cohort of Moderate-Severe Alzheimer’s Disease Patients and Show a Pro-Inflammatory Traffic…
2014
Alzheimer's disease (AD) is a progressive, irreversible, and debilitating disease for which no effective preventive or disease modifying therapies or treatments have so far been detected. The crucial step in AD pathogenesis is the production of amyloid-42 peptide, which causes chronic inflammation. Activated cells in the central nervous system (CNS) produce pro- inflammatory mediators that lead to the recruitment of myeloid or lymphocytic cells. As a consequence, the communication between the CNS and peripheral blood of AD subjects could influence the lymphocyte distribution and/or the expression of phenotypic markers. In the present paper, we show a significant decrease in total CD19 + B l…
The density and type of MECA-79-positive high endothelial venules correlate with lymphocytic infiltration and tumour regression in primary cutaneous …
2013
Aims Tumour-infiltrating lymphocytes have prognostic value in malignant melanoma. High endothelial venules (HEVs) are specialized vessels present in lymph nodes and tertiary lymphoid organs. CCL19, CCL21 and CCR7 regulate lymphocyte migration through HEVs. The aim of our study was to correlate HEV density in cutaneous primary and metastatic malignant melanomas with clinicopathological parameters, and with CCL19, CCL21 and CCR7 mRNA expression. Methods and results High endothelial venule density was evaluated by immunohistochemistry with a specific antibody, MECA-79, and chemokine expression was evaluated by real-time PCR. MECA-79-positive vessels, covered by cuboidal (C-HEV) or flat (F-HEV)…
Effect of Chemokine Receptors CXCR4 and CCR7 on the Metastatic Behavior of Human Colorectal Cancer
2005
AbstractPurpose: The expression of chemokine receptors CXCR4 and CCR7 has been associated with tumor dissemination and poor prognosis in a limited number of tumor entities. However, no data are currently available on the impact of chemokine receptor expression on disease progression and prognosis in human colorectal cancer.Experimental Design: The expression of CXCR4 and CCR7 was evaluated in 96 patients with histologically confirmed colorectal cancers and in four colorectal cancer cell lines by immunohistochemical staining. Furthermore, cell migration assays were done with SW480, SW620, and LS174T cancer cells to confirm the effect of the CXCR4 ligand stromal cell–derived factor 1α on migr…
Analysis of memory and effector CD8+ T cell subsets in chronic graft-versus-host disease.
2009
In humans, the selective depletion of CD8+ cells may prevent GVHD after allogeneic transplantation. These cells can infiltrate and damage target tissues. It is of interest to investigate the phenotypical characteristics and cytotoxic properties of the different CD8+ subsets in cGVHD patients. In a preliminary study we found that patients with cGVHD had a markedly elevated percentage of peripheral blood CCR7−/CD45RA+ cells compared to patients without cGVHD; conversely, the CCR7+/CD45RA+ subsets of CD8+ cells was significantly decreased. In this study, we report in depth on the phenotype of effector T cell subsets in cGVHD patients, as well as their proliferative capability, cytotoxic prope…