Cutting edge: Nociceptin stimulates neutrophil chemotaxis and recruitment:Inhibition by aspirin-triggered-15-epi-lipoxin A(4)

The nociceptin receptor (Noci-R) is a G protein-coupled receptor present in neural tissues and its activation by nociceptin is involved in the process ing of pain signals. Here, we report that Noci-R is present and functional on peripheral blood polymorphonuclear leukocytes (PMN), Human PMN express m RNA for Noci-R, its nucleotide sequence determined, and specific binding wi th [I-125]-labeled nociceptin gave an apparent K-d similar to1.5 nM for thi s PMN opioid receptor. Nociceptin evoked PMN chemotaxis with maximal activi ty at 100 pM, without intracellular Ca2+ mobilization, When injected in mur ine air pouches, nociceptin elicited leukocyte infiltration in a concentrat ion-dependent fashion. Nociceptin-stimulated PMN infiltration was inhibited by treating mice with is synthetic analog of the aspirin-triggered lipid m ediator 15-epi-lipoxin A(4). The present results identify nociceptin as a p otent chemoattractant and provide a novel link between the neural and immun e systems that are blocked by aspirin-triggered lipid mediators and may be relevant in neurogenic inflammation.