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Faculty of Science, Medicine and Health - Papers: part A

2013

Receptor

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Full-Text Articles in Social and Behavioral Sciences

Cay10593 Inhibits The Human P2x7 Receptor Independently Of Phospholipase D1 Stimulation, A Pupovac, L Stokes, R Sluyter Jan 2013

Cay10593 Inhibits The Human P2x7 Receptor Independently Of Phospholipase D1 Stimulation, A Pupovac, L Stokes, R Sluyter

Faculty of Science, Medicine and Health - Papers: part A

The P2X7 receptor is a trimeric ATP-gated cation channel important in health and disease. We have observed that the specific phospholipase D (PLD)1 antagonist, CAY10593 impairs P2X7-induced shedding of the 'low affinity' IgE receptor, CD23. The current study investigated the mode of action of this compound on P2X7 activation. Measurements of ATP-induced ethidium+ uptake revealed that CAY10593 impaired P2X7-induced pore formation in human RPMI 8226 B cells, P2X7-transfected HEK-293 cells and peripheral blood mononuclear cells. Concentration response curves demonstrated that CAY10593 impaired P2X7-induced pore formation in RPMI 8226 cells more potently than the PLD2 antagonist CAY10594 and the non-specific PLD …


Expression Of Proteins Within The Nogo Receptor Complex Are Altered In The Dorsolateral Prefrontal Cortex In Schizophrenia, J Andrews, K Newell, F Fernandez Jan 2013

Expression Of Proteins Within The Nogo Receptor Complex Are Altered In The Dorsolateral Prefrontal Cortex In Schizophrenia, J Andrews, K Newell, F Fernandez

Faculty of Science, Medicine and Health - Papers: part A

No abstract provided.


The Role Of Hypothalamic H1 Receptor Antagonism In Antipsychotic-Induced Weight Gain, Meng He, Chao Deng, Xu-Feng Huang Jan 2013

The Role Of Hypothalamic H1 Receptor Antagonism In Antipsychotic-Induced Weight Gain, Meng He, Chao Deng, Xu-Feng Huang

Faculty of Science, Medicine and Health - Papers: part A

Treatment with second generation antipsychotics (SGAs), notably olanzapine and clozapine, causes severe obesity side effects. Antagonism of histamine H1 receptors has been identified as a main cause of SGA-induced obesity, but the molecular mechanisms associated with this antagonism in different stages of SGA-induced weight gain remain unclear. This review aims to explore the potential role of hypothalamic histamine H1 receptors in different stages of SGA-induced weight gain/obesity and the molecular pathways related to SGA-induced antagonism of these receptors. Initial data have demonstrated the importance of hypothalamic H1 receptors in both short- and long-term SGA-induced obesity. Blocking hypothalamic H1 receptors by …


Molecular Evidence Of N-Methyl-D-Aspartate Receptor Hypofunction In Schizophrenia, C S. Weickert, S J. Fung, V S. Catts, P R. Schofield, K M. Allen, L T. Moore, Kelly A. Newell, D Pellen, Xu-Feng Huang, S V. Catts, T W Weickert Jan 2013

Molecular Evidence Of N-Methyl-D-Aspartate Receptor Hypofunction In Schizophrenia, C S. Weickert, S J. Fung, V S. Catts, P R. Schofield, K M. Allen, L T. Moore, Kelly A. Newell, D Pellen, Xu-Feng Huang, S V. Catts, T W Weickert

Faculty of Science, Medicine and Health - Papers: part A

Blockade of N-methyl-D-aspartate receptors (NMDARs) produces behavior in healthy people that is similar to the psychotic symptoms and cognitive deficits of schizophrenia and can exacerbate symptoms in people with schizophrenia. However, an endogenous brain disruption of NMDARs has not been clearly established in schizophrenia. We measured mRNA transcripts for five NMDAR subunit mRNAs and protein for the NR1 subunit in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia and control (n=74) brains. Five NMDAR single-nucleotide polymorphisms (SNPs) previously associated with schizophrenia were tested for association with NMDAR mRNAs in postmortem brain and for association with cognitive ability in an antemortem cohort …


Metabotropic Glutamate Receptor 5 Binding And Protein Expression In Schizophrenia And Following Antipsychotic Drug Treatment, Natalie Matosin, Elisabeth Frank, Chao Deng, Xu-Feng Huang, Kelly A. Newell Jan 2013

Metabotropic Glutamate Receptor 5 Binding And Protein Expression In Schizophrenia And Following Antipsychotic Drug Treatment, Natalie Matosin, Elisabeth Frank, Chao Deng, Xu-Feng Huang, Kelly A. Newell

Faculty of Science, Medicine and Health - Papers: part A

Metabotropic glutamate receptor 5 (mGluR5) has been identified as a potential therapeutic target for schizophrenia, primarily due to its ability to indirectly modulate glutamatergic signalling through the NMDA receptor (NMDAR). Despite its potential, molecular studies characterising mGluR5 in schizophrenia are limited. We therefore aimed to determine if the mGluR5 binding site or protein levels were altered in schizophrenia or by current antipsychotics. Using in-situ radioligand binding and immunoblot, we measured [3H]MPEP binding to mGluR5 and mGluR5 protein density in the post-mortem dorsolateral prefrontal cortex (DLPFC; BA46) of 37 schizophrenia and 37 matched control subjects. Subsequently, we measured [3H]MPEP binding in …


P2x7 Receptor Activation Induces Reactive Oxygen Species Formation In Erythroid Cells, Bin Wang, Ronald Sluyter Jan 2013

P2x7 Receptor Activation Induces Reactive Oxygen Species Formation In Erythroid Cells, Bin Wang, Ronald Sluyter

Faculty of Science, Medicine and Health - Papers: part A

The presence of P2X7 on erythroid cells is well established, but its physiological role remains unclear. The current study aimed to determine if P2X7 activation induces reactive oxygen species (ROS) formation in murine erythroleukaemia (MEL) cells, a commonly used erythroid cell line. ATP induced ROS formation in a time- and concentration-dependent fashion. The most potent P2X7 agonist, 2′(3′)-O-(4-benzoylbenzoyl)ATP, but not UTP or ADP, also induced ROS formation. The P2X7 antagonist, A-438079, impaired ATP-induced ROS formation. The ROS scavenger, N-acetyl-l-cysteine, and the ROS inhibitor, diphenyleneiodonium, also impaired P2X7-induced ROS formation, but use of enzyme-specific ROS inhibitors failed to identify the intracellular …


P2x7 Receptor Activation Induces Reactive Oxygen Species Formation And Cell Death In Murine Eoc13 Microglia, Rachael Bartlett, Justin J. Yerbury, Ronald Sluyter Jan 2013

P2x7 Receptor Activation Induces Reactive Oxygen Species Formation And Cell Death In Murine Eoc13 Microglia, Rachael Bartlett, Justin J. Yerbury, Ronald Sluyter

Faculty of Science, Medicine and Health - Papers: part A

The P2X7 purinergic receptor is a ligand-gated cation channel expressed on leukocytes including microglia. This study aimed to determine if P2X7 activation induces the uptake of organic cations, reactive oxygen species (ROS) formation, and death in the murine microglial EOC13 cell line. Using the murine macrophage J774 cell line as a positive control, RT-PCR, immunoblotting, and immunolabelling established the presence of P2X7 in EOC13 cells. A cytofluorometric assay demonstrated that the P2X7 agonists adenosine-5'-triphosphate (ATP) and 2' (3')-O-(4-benzoylbenzoyl) ATP induced ethidium(+) or YO-PRO-1(2+) uptake into both cell lines. ATP induced ethidium+ uptake into EOC13 cells in a concentration-dependent manner, with …


Human P2x7 Receptor Activation Induces The Rapid Shedding Of Cxcl16, Aleta Pupovac, Christopher M. Foster, Ronald Sluyter Jan 2013

Human P2x7 Receptor Activation Induces The Rapid Shedding Of Cxcl16, Aleta Pupovac, Christopher M. Foster, Ronald Sluyter

Faculty of Science, Medicine and Health - Papers: part A

Activation of the purinergic P2X7 receptor by extracellular ATP induces the shedding of cell-surface molecules including the low-affinity IgE receptor, CD23 from leukocytes. CD23 is a known substrate of a disintegrin and metalloprotease (ADAM)10. The aim of the current study was to determine if P2X7 activation induced the shedding of the chemokine CXCL16, an ADAM10 substrate. Using immunolabelling and flow cytometry we demonstrate that human RPMI 8226 multiple myeloma B cells, which have been previously shown to express P2X7, also express CXCL16. Flow cytometric and ELISA measurements of ATP-induced loss of cell-surface CXCL16 showed that ATP treatment of RPMI 8226 …