Search results for "Purinergic signalling"

Abacavir induces platelet-endothelium interactions by interfering with purinergic signalling: A step from inflammation to thrombosis.

2017

The controversy connecting Abacavir (ABC) with cardiovascular disease has been fuelled by the lack of a credible mechanism of action. ABC shares structural similarities with endogenous purines, signalling molecules capable of triggering prothrombotic/proinflammatory programmes. Platelets are leading actors in the process of thrombosis. Our study addresses the effects of ABC on interactions between platelets and other vascular cells, while exploring the adhesion molecules implicated and the potential interference with the purinergic signalling pathway. The effects of ABC on platelet aggregation and platelet-endothelium interactions were evaluated, respectively, with an aggregometer and a flo…

Abacavir Induces Arterial Thrombosis in a Murine Model.

2018

Background The purinergic system is known to underlie prothrombotic and proinflammatory vascular programs, making the profile of experimental actions demonstrated by abacavir compatible with thrombogenesis. However, direct evidence of a prothrombotic effect by the drug has been lacking. Methods The present study appraised the effects of abacavir in a well-validated animal model of arterial thrombosis. The role of ATP-P2X7 receptors in the actions of the drug was also assessed, and the actions of recognized vascular-damaging agents and other nucleoside reverse-transcriptase inhibitors (NRTIs) were evaluated and compared to those of abacavir. Results Abacavir dose-dependently promoted thrombu…

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

2015

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…

Endogenous adenosine inhibits hippocampal CA1 neurones: further evidence from extra- and intracellular recording.

1988

Extracellular and intracellular recordings from CA1 pyramidal neurones of rats in vitro were used to study the effects of endogenous and exogenously applied adenosine. The adenosine receptor antagonist, caffeine, enhanced the intracellular recorded e.p.s.p.-i.p.s.p. sequence evoked by stimulation of the stratum radiatum which is antagonized by exogenous adenosine. The late, potassium dependent i.p.s.p. was not antagonized. The adenosine uptake inhibitor, nitrobenzylthioinosine (NBTI), mimicked the effects of exogenously applied adenosine. The effects of NBTI and of exogenously applied adenosine were antagonized by caffeine in the same manner. Exposure to adenosine deaminase enhanced the evo…

A1 receptors mediate adenosine inhibitory effects in mouse ileum via activation of potassium channels.

2008

Abstract Aims We investigated the effects induced by exogenous adenosine on the spontaneous contractile activity of the longitudinal muscle of a mouse ileum, the receptor subtypes activated, the involvement of enteric nerves and whether opening of K + channels was a downstream event leading to the observed effects. Main methods Mechanical responses of the mouse ileal longitudinal muscle to adenosine were examined in vitro as changes in isometric tension. Key findings Adenosine caused a concentration-dependent reduction of the spontaneous contraction amplitude of the ileal longitudinal muscle up to its complete disappearance. This effect induced was markedly reduced by an A 1 receptor antago…

Adenosine A2A receptors in diffuse dermal fibrosis: pathogenic role in human dermal fibroblasts and in a murine model of scleroderma.

2006

Objective Adenosine regulates inflammation and tissue repair, and adenosine A2A receptors promote wound healing by stimulating collagen matrix production. We therefore examined whether adenosine A2A receptors contribute to the pathogenesis of dermal fibrosis. Methods Collagen production by primary human dermal fibroblasts was analyzed by real-time polymerase chain reaction, 14C-proline incorporation, and Sircol assay. Intracellular signaling for dermal collagen production was investigated using inhibitors of MEK-1 and by demonstration of ERK phosphorylation. In vivo effects were studied in a bleomycin-induced dermal fibrosis model using adenosine A2A receptor–deficient wild-type littermate …

Adenosine negatively regulates duodenal motility in mice: role of A1 and A2A receptors

2011

BACKGROUND AND PURPOSE Adenosine is considered to be an important modulator of intestinal motility. This study was undertaken to investigate the role of adenosine in the modulation of contractility in the mouse duodenum and to characterize the adenosine receptor subtypes involved. EXPERIMENTAL APPROACH RT-PCR was used to investigate the expression of mRNA encoding for A1, A2A, A2B and A3 receptors. Contractile activity was examined in vitro as changes in isometric tension. KEY RESULTS In mouse duodenum, all four classes of adenosine receptors were expressed, with the A2B receptor subtype being confined to the mucosal layer. Adenosine caused relaxation of mouse longitudinal duodenal muscle; …

Adenosine A2A and A2B Receptors Differentially Modulate Keratinocyte Proliferation: Possible Deregulation in Psoriatic Epidermis

2017

Adenosine is a potent regulator of inflammation and immunity, but the role of adenosine receptors in keratinocytes remains controversial. We determined that in addition to A2B receptors, human epidermal keratinocytes also express A2A receptors, although to a lower extent. Through the use of selective adenosine receptor agonists and antagonists, we showed that physiological concentrations of adenosine activate A2B receptors in normal human keratinocytes, inducing cell cycle arrest through the increase of intracellular calcium but not through cAMP signaling. In contrast, the selective activation of A2A receptors by CGS-21680 induces keratinocyte proliferation via p38–mitogen-activated protein…