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1 We have investigated the e ects of the adenosine A 2A receptor agonist CGS 21680 (0.01 ± 1 mM) on reactive oxidant production by, and elastase release from FMLP-activated human neutrophils, as well as on cytosolic Ca 2+¯u xes and intracellular concentrations of cyclic AMP. 2 Oxidant production, elastase release and cyclic AMP were assayed using lucigenin-enhanced chemiluminescence, colourimetric and radioimmunoassay procedures respectively, while cytosolic Ca 2+¯u xes were measured by fura-2 spectro¯uorimetry in combination with radiometric procedures which distinguish between net e ux and in¯ux of the cation. 3 Treatment of neutrophils with CGS 21680 did not a ect the FMLP-activated release of Ca 2+ from intracellular stores, but resulted in dose-related acceleration of the rate of decline in fura-2 uorescence, as well as decreases in both e ux and store-operated in¯ux of Ca 2+ , compatible with enhancement of resequestration of the cation by the endo-membrane Ca 2+ -ATPase. These e ects on neutrophil Ca 2+ handling were associated with increased intracellular cyclic AMP and with inhibition of oxidant production and release of elastase. 4 In contrast, treatment of neutrophils with the selective A 2A receptor antagonist, ZM 241385 (2.5 mM), prevented the transient increase in cyclic AMP in FMLP-activated neutrophils which was associated with delayed sequestration of incoming Ca 2+ during store-operated in¯ux. 5 The CGS 21680-mediated reduction of Ca 2+ e ux from FMLP-activated neutrophils was also antagonized by pretreatment of the cells with ZM 241385 (2.5 mM), as well as by thapsigargin (1 mM), an inhibitor of the endo-membrane Ca 2+ -ATPase. ZM 241385 also neutralized the cyclic AMP-elevating and anti-in¯ammatory interactions of CGS 21680 with neutrophils.

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