Release of adenosine from human sensitized lung fragments and its effect on antigen-induced mediator release.
Adenosine may play a role in asthma as a pro-inflammatory mediator. In this study, the release of adenosine from human sensitized lung fragments and its effect on antigen-induced histamine and leukotriene release has been explored. Antigen challenge increased histamine and leukotriene release five-fold but was without effect on adenosine release. In contrast, the adenosine deaminase inhibitor EHNA (10 microM) and the adenosine kinase inhibitor 5-iodotubericidin (10 microM) increased adenosine concentration 45-fold (P < or = 0.001; n = 4 patients). Of major interest was the finding that the non-selective, cell impermeant, adenosine antagonist pSPT (100 microM) decreased histamine and leukotriene release by 25% (P < or = 0.001) and 40%, respectively (P < or = 0.05; n = 9 patients). Additionally, the non-selective adenosine agonist NECA (10 microM) markedly inhibited antigen-induced leukotriene release by 80-90% (P < or = 0.001) and marginally inhibited histamine release by approximately 10% (P < or = 0.05; n = 9); the A2a-selective agonist DPMA (10 microM) was without effect on either histamine or leukotriene release. These results are consistent with adenosine having a biphasic effect on antigen-induced mediator release with low concentrations potentiating release and high concentrations inhibiting release. The overall stimulatory effect of endogenous adenosine supports the proposal that adenosine may act as a pro-inflammatory mediator in asthma.
Konnaris
K
K
Department of Pharmacology, University of Sydney, NSW, Australia.
Lloyd
H G
HG
Temple
D M
DM
D000241:Adenosine / Q000819:agonists / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D000941:Antigens / Q000276:immunology / Q000494:pharmacology*; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007114:Immunization; D066298:In Vitro Techniques; D015289:Leukotrienes / Q000378:metabolism; D008168:Lung / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism*; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D000941:Antigens; D015289:Leukotrienes; C056426:CGS 24012; D019830:Adenosine-5'-(N-ethylcarboxamide); C031433:8-(4-sulfophenyl)theophylline; D013806:Theophylline; D000241:Adenosine