Search results for "purinergic"

P1086 : Complex effects of adenosine receptor antagonists in models of liver fibrosis

2015

Control of enteric neuromuscular functions by purinergic P2X7 receptors in normal rat distal colon and experimental bowel inflammation

2013

Introduction: Purinergic signalling plays a pivotal role in the physiological regulation of several enteric functions, as well as in the modulation of immune/inflammatory cell activity. Recent evidence has shown an active involvement of the purinergic P2X7 receptor (P2X7R) in the fine tuning of immune functions, as well as its critical role in driving enteric neuron apoptosis under intestinal inflammation. However, the participation of this receptor pathway in the regulation of enteric neuromuscular functions remains undetermined. Aims: This study investigated the role of P2X7Rs in the control of colonic motility, both under normal conditions and in the presence of experimental colitis. Met…

Melittin Modulates Keratinocyte Function through P2 Receptor-dependent ADAM Activation

2012

Melittin, the major component of the bee venom, is an amphipathic, cationic peptide with a wide spectrum of biological properties that is being considered as an anti-inflammatory and anti-cancer agent. It modulates multiple cellular functions but the underlying mechanisms are not clearly understood. Here, we report that melittin activates disintegrin-like metalloproteases (ADAMs) and that downstream events likely contribute to the biological effects evoked by the peptide. Melittin stimulated the proteolysis of ADAM10 and ADAM17 substrates in human neutrophil granulocytes, endothelial cells and murine fibroblasts. In human HaCaT keratinocytes, melittin induced shedding of the adhesion molecu…

Neuroprotection elicited by P2Y13 receptors against genotoxic stress by inducing DUSP2 expression and MAPK signaling recovery.

2014

AbstractNucleotides activating P2Y13 receptors display neuroprotective actions against different apoptotic stimuli in cerebellar granule neurons. In the present study, P2Y13 neuroprotection was analyzed in conditions of genotoxic stress. Exposure to cisplatin and UV radiation induced caspase-3-dependent apoptotic cell death, and p38 MAPK signaling de-regulation. Pre-treatment with P2Y13 nucleotide agonist, 2methyl-thio-ADP (2MeSADP), restored granule neuron survival and prevented p38 long-lasting activation induced by cytotoxic treatments. Microarray gene expression analysis in 2MeSADP-stimulated cells revealed over-representation of genes related to protein phosphatase activity. Among them…

Alpha-defensins secreted by dysplastic granulocytes inhibit the differentiation of monocytes in chronic myelomonocytic leukemia.

2010

Abstract Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic disorder that occurs in elderly patients. One of the main diagnostic criteria is the accumulation of heterogeneous monocytes in the peripheral blood. We further explored this cellular heterogeneity and observed that part of the leukemic clone in the peripheral blood was made of immature dysplastic granulocytes with a CD14−/CD24+ phenotype. The proteome profile of these cells is dramatically distinct from that of CD14+/CD24− monocytes from CMML patients or healthy donors. More specifically, CD14−/CD24+ CMML cells synthesize and secrete large amounts of alpha-defensin 1-3 (HNP1-3). Recombinant HNPs inhibit macrophage co…

Interference with purinergic signalling

2016

Objective: The association of abacavir (ABC), a guanosine analogue, with cardiovascular toxicity is a long-lasting matter of controversy engendered by the lack of a mechanism of action. Clinical data point to an acute mechanism of vascular inflammation. Previous studies have shown that ABC induces leukocyte-endothelial cell interactions, an indicator of vascular inflammation. These effects are reproduced by another purine analogue, didanosine, but not by pyrimidine or acyclic nucleotide analogues, hinting at an interference with the purinergic system. The aim of the present study was to assess the role of ATP-receptors in leukocyte accumulation induced by ABC. Design and methods: Clinical c…

Inhibitory responses to exogenous adenosine in murine proximal and distal colon”

2006

The aims of the present study were firstly, to characterize pharmacologically the subtypes of P(1) purinoreceptors involved in the inhibitory effects induced by exogenous adenosine in longitudinal smooth muscle of mouse colon, and secondly, to examine differences in the function and distribution of these receptors between proximal and distal colon. Adenosine (100 microM-3 mM) caused a concentration-dependent reduction of the amplitude of spontaneous contractions in the proximal colon, and muscular relaxation in the distal colon. In the proximal colon, adenosine effects were antagonized by a selective A(1) receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 10 nM), but were not m…

Negative regulation of diacylglycerol kinase θ mediates adenosine-dependent hepatocyte preconditioning

2010

In liver ischemic preconditioning (IP), stimulation of adenosine A2a receptors (A2aR) prevents ischemia/reperfusion injury by promoting diacylglycerol-mediated activation of protein kinase C (PKC). By concerting diacylglycerol to phosphatidic acid, diacylglycerol kinases (DGKs) act as terminator of diacylglycerol signalling. This study investigates the role of DGK in the development of hepatocyte IP. DGK activity and cell viability were evaluated in isolated rat hepatocytes preconditioned by 10 min hypoxia followed by 10 min re-oxygenation or by the treatment with the A2aR agonist, CGS21680, and subsequently exposed to prolonged hypoxia. We observed that after IP or A2aR activation, a decre…

Alterations in striatal neuropeptide mRNA produced by repeated administration of L-DOPA, ropinirole or bromocriptine correlate with dyskinesia induct…

2002

Chronic administration of L-DOPA to MPTP-treated common marmosets induces marked dyskinesia while repeated administration of equivalent antiparkisonian doses of ropinirole and bromocriptine produces only mild involuntary movements. The occurrence of dyskinesia has been associated with an altered balance between the direct and indirect striatal output pathways. Using in situ hybridisation histochemistry, we now compare the effects of these drug treatments on striatal preproenkephalin-A (PPE-A) and adenosine A(2a) receptor mRNA expression as markers of the indirect pathway and striatal preprotachykinin (PPT) mRNA and preproenkephalin-B (PPE-B, prodynorphin) mRNA expression as markers of the d…

Functional role of cholinoceptors and purinoceptors in human isolated atrial and ventricular heart muscle

1989

1. The effects of cholinergic and purinergic stimulation on action potential, force of contraction and 86Rb efflux were investigated in human atrial and ventricular heart muscle. 2. In atrial heart muscle, carbachol and (-)-N6-(R-phenyl-isopropyl)-adenosine (R-PIA) and 5'-(N-ethyl)-carboxamido-adenosine (NECA) evoked transient decreases of action potential duration and force of contraction; the steady-state effects on force of contraction were virtually identical to control values. In the presence of propranolol, steady-state values after carbachol, R-PIA or NECA amounted to about 50% of control values. 3. In ventricular heart muscle, carbachol, NECA and R-PIA did not significantly affect t…