A1 Receptor Research Articles

Abnormal functional lateralization and cooperation in bipolar disorder are associated with neurotransmitter and cellular profiles

BackgroundHemispheric lateralization and cooperation are essential for efficient brain function, and aberrations in both have been found in psychiatric disorders such as schizophrenia. This study investigated alterations in hemispheric lateralization and cooperation among patients with bipolar disorder (BD) and associations with neurotransmitter and cell-type density distributions to identify potential molecular and cellular pathomechanisms. MethodsSixty-seven BD patients and 127 healthy controls (HCs) were examined by resting-state functional MRI (rs-fMRI). Whole-brain maps of the autonomy index (AI) and connectivity between functionally homotopic voxels (CFH) were constructed to reveal BD-specific changes in brain functional lateralization and interhemispheric cooperation, respectively. Spatial associations of regional AI and CFH abnormalities with neurotransmitter and cell-type density distributions were examined by correlation analyses. ResultsBipolar disorder patients exhibited higher AI values in left superior parietal gyrus, cerebellar right Crus I, and cerebellar right Crus II, and these regional abnormalities were associated with the relative densities (proportions) of oligodendrocyte precursor cells and microglia. Patients also exhibited lower CFH values in right inferior parietal gyrus, bilateral middle occipital gyrus, left postcentral gyrus, and bilateral cerebellar crus II, and these regional abnormalities were associated with the densities of serotonin 1A and dopamine D2 receptors, oligodendrocyte precursor cells, astrocytes, and neurons. ConclusionsThese findings indicate that abnormal functional lateralization and cooperation in BD with potential molecular and cellular basis.

A1 adenosine receptor evoked Ca2+ signals in astrocytes

Abstract In addition to neurons, glial cells make up the nervous system. These glial cells are divided into macroglial cells - including astrocytes - and microglial cells. Astrocytes have several important functions in the central nervous system, such as synthesizing transmitters and releasing them, thereby activating the surrounding neurons and astrocytes. Astrocytes do not generate action potentials, but they can transmit information to neighboring cells and react to external stimuli by employing Ca2+ dynamics. Increased neuronal activity can lead to an increased extracellular level of adenosine, reflected by a change in the metabolic state. Adenosine is a naturally occurring nucleoside distributed throughout the body as a metabolic intermediary. Its action is mediated by binding to adenosine receptors, such as the G-protein coupled receptors (GPCRs) A1 adenosine receptor. The binding of adenosine to the specific receptor type activates different signaling pathways in astrocytes. In our work, we studied Ca2+ signals generated upon adenosine A1 receptor activation by adding the pathway to the computational astrocyte model by Oschmann et.al (2017). We investigated the influence of the high-affinity A1 adenosine receptor in various astrocyte domains on the regulated Ca2+ release from the endoplasmic reticulum (ER) of astrocytes and concluded that the receptor-dependent pathway contributes to Ca2+ signals mainly in the soma.

Characterization of the Immune-Dominant Region on the CysR Domain of Phospholipase A2 Receptor 1 (PLA2R1) Targeted by Autoreactive Memory B Cells

Characterization of the Immune-Dominant Region on the CysR Domain of Phospholipase A2 Receptor 1 (PLA2R1) Targeted by Autoreactive Memory B Cells

Different Dosage Regimens of Rituximab in Primary Membranous Nephropathy Treatment: A Systematic Review.

Primary membranous nephropathy (PMN) is one of the prevalent pathological types of adult primary nephrotic syndrome. Pathogenic autoantibodies targeting podocyte antigens such as phospholipase A2 receptor (PLA2R) lead to the disease. Patients frequently experience notable adverse effects when treated with conventional immunosuppressive therapies. Rituximab (RTX), a mouse/human monoclonal antibody, selectively depletes B cells and leads to a decrease in the antibody levels in the circulation, which helps to alleviate membranous nephropathy. Various RTX dosage regimens have been applied globally in the PMN treatment with satisfactory effects. Nevertheless, the optimal dosage of RTX has yet to be determined. This article reviews the application of different doses of RTX in the management of PMN so far.

Anti-phospholipase A2 Receptor (PLA2R)-Positive Membranous Nephropathy Triggered by Sunitinib in Patients with Gastrointestinal Stromal Tumor (GIST): A New Association?

Anti-phospholipase A2 Receptor (PLA2R)-Positive Membranous Nephropathy Triggered by Sunitinib in Patients with Gastrointestinal Stromal Tumor (GIST): A New Association?

Phospholipase A2 Receptor (PLA2R)-Positive Membranous Nephropathy by Laser Microdissection and Mass Spectrometry in Patients with Negative Routine Immunofluorescence Microscopy for PLA2R on Kidney Biopsy

Phospholipase A2 Receptor (PLA2R)-Positive Membranous Nephropathy by Laser Microdissection and Mass Spectrometry in Patients with Negative Routine Immunofluorescence Microscopy for PLA2R on Kidney Biopsy

Assessing the Utility and Accuracy of Phospholipase A2 Receptor (PLA2R) Antibody in Membranous Nephropathy: A Systematic Review and Meta-Analysis

Assessing the Utility and Accuracy of Phospholipase A2 Receptor (PLA2R) Antibody in Membranous Nephropathy: A Systematic Review and Meta-Analysis

Overview of the Characteristics of a Phospholipase A2 Receptor (PLA2R)-Negative Membranous Nephropathy Cohort

Overview of the Characteristics of a Phospholipase A2 Receptor (PLA2R)-Negative Membranous Nephropathy Cohort

Urine IgG4 May Be a Specific Biomarker to Monitor the Progression of Phospholipase A2 Receptor (PLA2R)-Positive Primary Membranous Glomerulopathy (pMGN)

Urine IgG4 May Be a Specific Biomarker to Monitor the Progression of Phospholipase A2 Receptor (PLA2R)-Positive Primary Membranous Glomerulopathy (pMGN)

Effect of Phospholipase A2 Receptor (PLA2R) Antibody and Inflammatory Factors on Cardiovascular and Thromboembolic Events in Patients with Primary Membranous Nephropathy

Effect of Phospholipase A2 Receptor (PLA2R) Antibody and Inflammatory Factors on Cardiovascular and Thromboembolic Events in Patients with Primary Membranous Nephropathy

CD19 Repopulation and Anti-phospholipase A2 Receptor (PLA2R) following Rituximab in Membranous Nephropathy

CD19 Repopulation and Anti-phospholipase A2 Receptor (PLA2R) following Rituximab in Membranous Nephropathy

The role of kidney biopsy in the diagnosis of membranous nephropathy.

The discovery of the target antigen M-type phospholipase A2 receptor (PLA2R) with the possibility to detect anti-PLA2R antibodies in serum as well as the identification of several other antigens, overall accounting for almost all cases of membranous nephropathy, paved the way to a revolutionary change in the classification of membranous nephropathy. Serum anti-PLA2R autoantibody titers have been found to be highly specific diagnostic and prognostic biomarkers. Therefore, a positive test for anti-PLA2R serology in patients who present with nephrotic syndrome, normal kidney function, and no evidence of another process to account for proteinuria is believed to suffice to make a diagnosis of primary membranous nephropathy, thus removing the need for a renal biopsy. While technological advances will likely allow this proposal to prevail in the near future, the reasons why renal biopsy could still remain a critical tool for the management of membranous nephropathy in real life are discussed.

Double Trouble in the Basement! A Case of Phospholipase A2 Receptor (PLA2R)-Associated Membranous Nephropathy with Atypical Anti-glomerular Basement Membrane Disease

Double Trouble in the Basement! A Case of Phospholipase A2 Receptor (PLA2R)-Associated Membranous Nephropathy with Atypical Anti-glomerular Basement Membrane Disease

Phospholipase A2 Receptor (PLA2R)-Positive Membranous Nephropathy in a Patient with Negative PLA2R Serology

Phospholipase A2 Receptor (PLA2R)-Positive Membranous Nephropathy in a Patient with Negative PLA2R Serology

Assessment of Endothelial Dysfunction in Patient with Phospholipase A2 Receptor (PLA2R)-Positive Primary Membranous Nephropathy in Remission

Assessment of Endothelial Dysfunction in Patient with Phospholipase A2 Receptor (PLA2R)-Positive Primary Membranous Nephropathy in Remission

Comparability of Two Anti-phospholipase A2 Receptor (PLA2R) Enzyme-Linked Immunosorbent Assays (ELISAs) in Patients with Primary Membranous Nephropathy

Comparability of Two Anti-phospholipase A2 Receptor (PLA2R) Enzyme-Linked Immunosorbent Assays (ELISAs) in Patients with Primary Membranous Nephropathy

Ultra-low doses of methamphetamine suppress 5-hydroxytryptophan-induced head-twitch response in mice during aging.

The head-twitch response (HTR) in mice is considered a behavioral assay for activation of 5-HT 2A receptors in rodents. It can be evoked by direct-acting 5-HT 2A receptor agonists such as (±)-2,5-dimethoxy-4-iodoamphetamine, 5-hydroxytryptamine precursors [e.g. 5-hydroxytryptophan (5-HTP)], and selective 5-hydroxytryptamine releasers (e.g. d -fenfluramine). The nonselective monoamine releaser methamphetamine by itself does not produce the HTR but can suppress both (±)-2,5-dimethoxy-4-iodoamphetamine- and d -fenfluramine-evoked HTRs across ages via concomitant activation of the inhibitory serotonergic 5-HT 1A or adrenergic α 2 receptors. Currently, we investigated: (1) the ontogenic development of 5-HTP-induced HTR in 20-, 30-, and 60-day-old mice; (2) whether pretreatment with ultra-low doses of methamphetamine (0.1, 0.25, and 0.5 mg/kg, intraperitoneally) can suppress the frequency of 5-HTP-induced HTR at different ages; and (3) whether the inhibitory serotonergic 5-HT 1A or adrenergic α 2 receptors may account for the potential inhibitory effect of methamphetamine on 5-HTP-induced HTR. In the presence of a peripheral decarboxylase inhibitor (carbidopa), 5-HTP produced maximal frequency of HTRs in 20-day-old mice which rapidly subsided during aging. Methamphetamine dose-dependently suppressed 5-HTP-evoked HTR in 20- and 30-day-old mice. The selective 5-HT 1A -receptor antagonist WAY 100635 reversed the inhibitory effect of methamphetamine on 5-HTP-induced HTR in 30-day-old mice, whereas the selective adrenergic α 2 -receptor antagonist RS 79948 failed to reverse methamphetamine's inhibition at any tested age. These findings suggest an ontogenic rationale for methamphetamine's inhibitory 5-HT 1A receptor component of action in its suppressive effect on 5-HTP-induced HTR during development which is not maximally active at a very early age.

124 - The serotonin 2A receptor is involved in the hypersensitivity of bladder afferent neurons in cyclophosphamide-induced cystitis

124 - The serotonin 2A receptor is involved in the hypersensitivity of bladder afferent neurons in cyclophosphamide-induced cystitis

Stress enhances aggression in male rats with genetic stress hyper-reactivity.

The current study investigated stress-induced aggressive behavior in the resident-intruder test in males of the genetically stress hyper-reactive Wistar Kyoto More Immobile (WMI), and the nearly isogenic, control Wistar Kyoto Less Immobile (WLI) strains. Tests were carried out against same-age intruders during adolescence, and same-age and juvenile intruders in adulthood. In adolescence and adulthood, prior acute restraint stress decreased social interactions and decreased aggressive behaviors of adolescents and adult WLIs. However, prior stress precipitated aggression in the adult WMI males toward both same-age, and juvenile intruders compared with control WMIs and WLIs. Trunk blood levels of testosterone and androstenedione increased in stressed WLIs, but not in WMIs, suggesting no direct role of androgens in the increased aggression of WMIs. Expressions of aggression-relevant genes showed patterns commensurate with being causative in aggressive behavior. The methyl-CpG binding protein 2 was lower in the frontal cortex of control WMIs, and in the amygdala of stressed WMIs compared with their respective WLIs. Frontal cortex expression of vasopressin receptor 1a and serotonin transporter increased, solely in WMI males after stress. As behaviors were the same toward same-age and non-threatening juvenile intruders, the stress-induced increase in confrontational behavior of the adult WMI male was not because of enhanced fear or anxiety. These results suggest that genetic stress hyper-reactivity is a risk factor for stress-induced increases in aggression in males. Additionally, as known aggression-related genes showed expression patterns paralleling aggressive behavior, this model system could identify novel molecular pathways leading to stress-enhanced aggression.

Molecular mechanisms of transmitted endoplasmic reticulum stress mediating immune escape of gastric cancer via PVR overexpression in TAMs

Gastric cancer (GC) is the fourth leading cause of cancer death worldwide. Due to the complex tumor microenvironment (TME), the efficacy of immunotherapy in GC has not met expectations. Malignant changes in the TME induce endoplasmic reticulum stress (ERS). ERS can be transmitted between tumor cells and tumor-associated macrophages (TAMs), promoting tumor immune escape, but the specific mechanism in GC remains unclear. We established a TAM model of transmitted ERS (TERS), and iTRAQ proteomic analysis identified overexpressed proteins. The overexpression of poliovirus receptor (PVR) was screened while flow cytometry and ELISA showed that PVR mediated the immunosuppressive function of TAMs by downregulating the proliferative activity and cytotoxicity of cocultured CD8+ T lymphocytes. With EMSA and dual-luciferase reporter assays, we confirmed that erythropoietin-producing hepatocellular receptor A2 (EphA2) affected PVR expression by increasing the transcriptional activity of activator protein-1 (AP-1). MFC cells were mixed with EphA2 knockdown or control RAW264.7 cells to establish subcutaneous tumor models with or without tunicamycin treatment in vivo. The vivo experiments revealed that ERS promoted subcutaneous xenograft growth, which was reversed by EphA2 knockdown. Clinically, GC patients with high expression of PVR and EphA2 tended to have an immunosuppressive TME, which were determined by immunohistochemical and immunofluorescence analyses. In conclusion, the transcriptional activity of AP-1 is upregulated in ERS-transmitted TAMs through EphA2 to increase PVR expression, which promotes immune escape in GC. Our study provides a new perspective on the role of ERS in tumor immunity.