Gourine, AV and Poputnikov, DM and Zhernosek, N and Melenchuk, EV and Gerstberger, R and Spyer, KM and Gourine, VN (2005) P2 receptor blockade attenuates fever and cytokine responses induced by lipopolysaccharide in rats. BRIT J PHARMACOL , 146 (1) 139 - 145. 10.1038/sj.bjp.0706287.
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1 Adenosine 5'-triphosphate (ATP) has been shown to induce release of cytokines implicated in fever, including interleukin(IL)-1 beta, IL-6, and tumour necrosis factor-alpha (TNF-alpha). The role of ATP-mediated purinergic signalling in fever and cytokine release during systemic inflammation was investigated by studying the effects of P2 receptor antagonists suramin, pyridoxal-5'phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), and Brilliant Blue G (BBG) on changes in body temperature and the increases in plasma levels of IL-1 beta, IL-6, and TNF alpha induced by bacterial lipopolysaccharide (LPS) in rats.2 LPS (Escherichia coli; 50 mu g kg(-1))-induced febrile response was attenuated by suramin (25 mg kg(-1) and 100 mg kg(-1)), PPADS (25 mg kg(-1)), and a more selective P2X(7) receptor antagonist BBG (100 mg kg(-1)) injected intraperitoneally before the induction of fever.3 The increase in plasma concentrations of IL-1 beta and IL-6, measured 1 h after LPS treatment, was reduced by PPADS (25 mu g kg(-1)) and BBG (100 mg kg(-1)). LPS-induced increase in plasma TNF-alpha concentration was also markedly attenuated by BBG (100 mg kg(-1)), but not by PPADS (25 mg kg(-1)).4 These data indicate that purinergic signalling plays an important role in the mechanisms responsible for the LPS-induced febrile response and increases in the levels of circulating cytokines. We suggest that ATP acting via P2X(7) receptors induces release of pyrogenic cytokines to mediate fever during systemic inflammation.
|Title:||P2 receptor blockade attenuates fever and cytokine responses induced by lipopolysaccharide in rats|
|Keywords:||ATP, body temperature, Brilliant Blue G, fever, interleukin-1 beta, interleukin-6, P2X(7) receptors, pyridoxal-5 '-phosphate-6-azophenyl-2 ',4 '-disulphonic acid, suramin, tumour necrosis factor-alpha, TUMOR-NECROSIS-FACTOR, FACTOR-ALPHA RELEASE, P2X(7) RECEPTOR, EXTRACELLULAR ATP, ACTIVATION, INTERLEUKIN-1-BETA, STIMULATION, MECHANISMS, IL-1-BETA, MICROGLIA|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Neuroscience, Physiology and Pharmacology|
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