2,528 research outputs found
THE P2Y-LIKE PURINERGIC/CYSTEINYL- LEUKOTRIENE RECEPTOR GPR17 AS A TARGET FOR BRAIN REPAIR IN NEURODEGENERATIVE DISEASES
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Different pathways of apoptosis revealed by 2-chloro-adenosine and deoxy-D-ribose in mammalian astroglial cells
No full textBoth the adenosine analogue 2-chloro-adenosine (2-CA) and the reducing sugar deoxy-D-ribose (dRib) induce apoptosis of astroglial cells in rat brain primary cultures (Abbracchio et al.: Biochem Biophys Res Commun 213:908-915, 1995), The present study was undertaken to elucidate by both morphological and cytofluorimetric analyses the intracellular mechanism(s) involved in induction of apoptosis by these two agents, The poly(ADP-ribose)polymerase (PARP) inhibitor 3-aminobenzamide did not prevent either 2-CA- or dRib-induced cell death, suggesting that activation of PARP is not critically important for induction of apoptosis in astrocytes. The radical scavenger N-acetyl-cysteine (NAG) strongly inhibited dRib- but not 2-CA-induced cell death, suggesting a differential role for radical formation in apoptosis by these two agents, A time-dependent increase of cells with depolarized mitochondria was observed in dRib-, and to a lesser extent, in 2-CA-treated cultures, NAC also prevented dRib- but not 2-CA-induced mitochondrial changes, We conclude that, in mammalian astrocytes, apoptosis can proceed through diverse and multiple pathways, depending upon the apoptotic stimulus, For dRib, apoptosis likely proceeds through generation of radicals and mitochondrial involvement, An adenosine extracellular receptor linked to an as yet unidentified signaling pathway may instead mediate 2-CA-induced cell death, which may have intriguing implications for both nervous system development and brain response to trauma and ischemia
Towards a revised nomenclature for P1 and P2 receptors
No full textThe classification of receptors for adenosine, ATP and ADP (collectively called purinoceptors) has seen a number of developments in the past three years. The important division of receptors into two major classes (1) adenosine (P1) receptors and (2) P2 purinoceptors, first suggested by Burnstock in 1978 (Ref.2), has been an abiding one that has set the stage for further subdivision of P2 purinoceptors into P2X and P2Y subtypes on the basis of pharmacological properties. Later, Dubyak summarized the evidence that ATP worked through two different transduction mechanisms: intrinsic ion channels and G protein-coupled receptors. This information, coupled with the cloning of purinoceptors in 1993/94, led Abbracchio and Burnstock to propose that purinoceptors should be classified in two families: G protein-coupled receptors termed P2Y purinoceptors, and intrinsic ion channels termed P2X purinoceptors. Developments in recent years have borne out these expectations and a revised nomenclature, essentially adopting the Abbracchio and Burnstock proposal, can now be proposed
Purinergic signalling in inflammation of the central nervous system
No full textInflammation is the most fundamental body reaction to noxious stimuli. No vascularized tissue, organ or apparatus is free from this response. Several mediators of inflammation, originating from outside (exogenous) or inside (endogenous) the body, are known. Among the endogenous factors, extracellular nucleotides and nucleosides are attracting interest for their ubiquity and striking ability to modulate diverse immune responses. Until recently, it was doubted that the central nervous system (CNS), reportedly an 'immunoprivileged organ', could be the site of immune reactions. Nowadays, it is acknowledged that inflammation and immunity have a key role in a vast range of CNS diseases. Likewise, it is clear that purinergic signalling profoundly affects neuroinflammation. Here, we provide a brief update of the state of the art in this expanding field
Short-term TNF-alpha treatment induced A2B adenosine receptor desensitization in human astroglial cells
No full textLong-term glial cell treatment with the proinflammatory cytokine TNF-alpha has been demonstrated to increase the functional responsiveness of A 2B adenosine receptors (A2B ARs), which in turn synergize with the cytokine inducing chronic astrogliosis. In the present study, we investigated the short-term effects of TNF-alpha on A2B AR functional responses in human astroglial cells (ADF), thus simulating the acute phase of cerebral damage which is characterized by both cytokine and adenosine high level release. Short-term TNF-alpha cell treatment caused A2B AR phosphorylation inducing, in turn, impairment in A2B AR-G protein coupling and cAMP production. These effects occurred in a time-dependent manner with a maximum following 3-h cell exposure. Moreover, we showed PKC intracellular kinase is mainly involved in the TNF-alpha-mediated regulation of A2B AR functional responses. The results may indicate the A 2B AR functional impairment as a cell defense mechanism to counteract the A2B receptor-mediated effects during the acute phase of brain damage, underlying A2B AR as a target to modulate early inflammatory responses. © 2007 Wiley-Liss, Inc
PHARMACOLOGICAL CHARACTERIZATION OF P2X AND P2Y PURINOCEPTORS IN RAT BLADDER SMOOTH-MUSCLE AND EPITHELIUM
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