title: Nociceptin/orphanin FQ stimulates human monocyte chemotaxis via NOP receptor activation.
abstract: 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 (O2-) production from neutrophils. fMLP stimulated all the leukocyte functions examined. N/OFQ stimulated monocyte (pEC50 12.15) but not neutrophil chemotaxis. The production of O2- 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 [Arg14, Lys15]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. [Arg14, Lys15]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: [Arg14, Lys15]N/OFQ (pEC50 13.22)>Ro 64-6198 (pEC50 12.96)>N/OFQ(1-13)NH2 (pEC50 12.67)>N/OFQ (pEC50 12.15). Moreover, the monocyte chemoattractant action of N/OFQ was not modified by naloxone 1 microM while antagonized by UFP-101 10 microM (pA2 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ferrara, via Fossato di Mortara, 19, 44100 Ferrara, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Trombella
authors.forename: R
authors.initials: R
authors.lastname: Vergura
authors.forename: S
authors.initials: S
authors.lastname: Falzarano
authors.forename: R
authors.initials: R
authors.lastname: Guerrini
authors.forename: G
authors.initials: G
authors.lastname: Calo
authors.forename: S
authors.initials: S
authors.lastname: Spisani
mesh_terms: D002633:Chemotaxis / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018847:Opioid Peptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D009240:N-Formylmethionine Leucyl-Phenylalanine; D018847:Opioid Peptides; D010446:Peptide Fragments; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722283:OPRL1 protein, human