Nociceptin/orphanin FQ stimulates human monocyte chemotaxis via NOP receptor activation

Nociceptin/orphanin FQ (N/OFQ) produces several biological actions by activating the N/OFQ peptide receptor (NOP). It has been previously shown that N/OFQ stimulates leukocyte chemotaxis both in vitro and in vivo. In the present study we investigated the ability of N/OFQ, in comparison with the proinflammatory peptide formyl-Met-Leu-Phe (fMLP), to stimulate human neutrophil and monocyte chemotaxis and the release of lysozyme and superoxide anion (02) production from neutrophils. IMLP stimulated all the leukocyte functions examined. N/OFQ stimulated monocyte (pEC(50) 12.15) but not neutrophil chemotaxis. The production of O-2(-) from neutrophils was not affected by N/OFQ while the release of lysozyme was increased in a concentration dependent manner (pEC50 11.00) although the maximal effects evoked by N/OFQ were about half of those of fMLP. The NOP ligands [Arg(14), Lys(15)] N/OFQ, N/OFQ(1-13)NH2, Ro 64-6198, UFP-101 and the opioid antagonist naloxone were used for pharmacologically characterizing the receptor involved in the monocyte chemoattractant action of N/OFQ. [Arg(14), Lys(15)]N/OFQ, N/OFQ(1-13)NH2, and Ro 64-6198 mimicked the action of N/OFQ showing similar maximal effects and the following order of potency: [Arg(14), Lys(15)]N/OFQ (pEC(50) 113.22) > Ro 64-6198 (pEC(50) 12.96) > N/OFQ(1-13)NH2 (pEC50 12.67) > N/OFQ (pEC(50) 12.15). Moreover, the monocyte chemoattractant action of N/OFQ was not modified by naloxone 1 mu M while antagonized by UFP-101 10 mu M (pA(2) 7.00). Thus, the order of potency of agonists and the antagonist selectivity demonstrated that N/OFQ stimulates human monocyte chemotaxis via NOP receptor activation. (c) 2005 Published by Elsevier Inc.