%0 Journal Article
%T NOP Receptor Ligands as Potential Agents for Inflammatory and Autoimmune Diseases
%A Elaine C. Gavioli
%A Pedro R. T. Rom£¿o
%J Journal of Amino Acids
%D 2011
%I Hindawi Publishing Corporation
%R 10.4061/2011/836569
%X Nociceptin/orphanin FQ (N/OFQ) is a seventeen-amino acid peptide that is the endogenous ligand of a G-protein-coupled receptor (NOP). Various immune cells express the precursor protein and secrete N/OFQ as well as display binding sites for this peptide. The functional capacity of NOP receptor was demonstrated in vitro and in vivo studies by the ability of N/OFQ to induce chemotaxis of immune cells, to regulate the expression of cytokines and other inflammatory mediators, and to control cellular and humoral immunity. In this context, N/OFQ could modulate the outcome of some inflammatory diseases, such as sepsis and autoimmune pathologies by mechanisms not clearly elucidated yet. In fact, human body fluid revealed increased levels of N/OFQ under sepsis, arthritis, and Parkinson's diagnose. Preclinical studies pointed to the blockade of NOP receptor signaling as successful in treating these experimental conditions. Further preclinical and clinical studies are required to investigate the potential of NOP ligands in treating inflammatory diseases. 1. N/OFQ and NOP Receptor The peptide nociceptin/orphanin FQ (N/OFQ) was isolated for the first time in 1995 by two distinct research groups from rat [1] and porcine [2] brain extracts. N/OFQ is composed by seventeen amino acids residues, and this peptide was nominated nociceptin due to the hyperalgesic effects that it evokes after supraspinal administration [1]. The other name, orphanin FQ, was given by the Reinscheid¡¯s group due to the fact that this peptide displayed affinity to an orphan receptor¡ªactually, this was one of the first well-experienced cases of reversal pharmacology; while F and Q were used to discriminate the amino acids phenylalanine from the N-terminal and glutamine located in the C-terminal position [2]. N/OFQ is a neuropeptide sharing sequence homology with classical opioid peptides, but with a distinct pharmacological profile. N/OFQ was being considered an opioid-like peptide, since it is structurally related to endogenous opioids, particularly dynorphin A; however, N/OFQ does not bind to classical opioid receptors [2]. Additionally, N/OFQ is the endogenous ligand for the N/OFQ peptide (NOP) receptor (nominated before as opioid receptor like-1, abbreviated as ORL-1), which is closely related to the opioid receptor family, but does not bind opioid ligands [3]. NOP, similar to the opioid family, is a receptor coupled to a G-protein. Thus, the activation of the N/OFQ signaling via NOP receptor can lead, among other effects, to inhibition of adenylate cyclase, blockade of Ca2+, and opening of K+
%U http://www.hindawi.com/journals/jaa/2011/836569/