Adenosine inhibits superoxide production in rat peritoneal macrophages via elevation of cAMP level.
As a part of host-defense immune system, macrophages can response to a variety of stimulants and produce superoxide. We examined the effect of adenosine as a modulator on superoxide production induced by phorbol ester in rat peritoneal macrophages, using an acetyl-cytochrome c reduction method for its detection. 2-Cl-adenosine, a least metabolizable analog of adenosine, inhibited the superoxide production in a dose-dependent manner, and also showed the increasing effect on intracellular cAMP level. Superoxide production was also inhibited by the several reagents which increased intracellular cAMP level, including dibutyryl-cAMP. 8-bromo-cAMP (cell permeable cAMP analogs), forskolin (an adenyl-cyclase activator). Ro 20-1724 (an phosphodiesterase inhibitor), and propentofylline (a xanthine derivative), but not 8-bromo-cGMP (cell permeable cGMP analog). These results suggest that a high level of extracellular adenosine may attenuate immunity through regulating macrophage functions. On the other hand, the tissue damage which is resulted from an over-production of superoxide can be protected by adenosine and its related drugs via an elevation of intracellular cAMP level.
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Department of Physiology, Ehime University School of Medicine, Japan.
Nakamura
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Kataoka
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D015762:2-Chloroadenosine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004789:Enzyme Activation; D007424:Intracellular Fluid / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism*; D014970:Xanthines / Q000494:pharmacology
D014970:Xanthines; D013481:Superoxides; D015762:2-Chloroadenosine; D015124:8-Bromo Cyclic Adenosine Monophosphate; C032114:propentofylline; D003994:Bucladesine; D000242:Cyclic AMP; D011493:Protein Kinase C; D000241:Adenosine