Nociceptin modulates intracellular cAMP levels in PMNs. PMNs were incubated in the presence of adenosine deaminase (0.1 U/mL) to eliminate extracellular adenosine and stimulated with fMLP (100 nM) at t = 0 min in the presence of CGS 21680, a specific agonist of the adenosine A2A receptor subtype, and with Ro 20-1724, an inhibitor of phosphodiesterase IV. When present, nociceptin or the synthetic NociR agonist, Ro 64-6198, were added to cell suspensions at t = −1 min. Reactions were stopped at the indicated time points, and intracellular cAMP levels were determined as described in the Materials and Methods. Results represent one experiment, typical of three independent sets of experiments performed with PMNs from different donors.