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Pharmacology of nociceptin and its receptor: a novel therapeutic target Calo' G; Guerrini R; Rizzi A; Salvadori S; Regoli DBr J Pharmacol 2000[Apr]; 129 (7): 1261-83Nociceptin (NC), alias Orphanin FQ, has been recently identified as the endogenous ligand of the opioid receptor-like 1 receptor (OP(4)). This new NC/OP(4) receptor system belongs to the opioid family and has been characterized pharmacologically with functional and binding assays on native (mouse, rat, guinea-pig) and recombinant (human) receptors, by using specific and selective agonists (NC, NC(1 - 13)NH(2)) and a pure and competitive antagonist, [Nphe(1)]NC(1 - 13)NH(2). The similar order of potency of agonists and affinity values of the antagonist indicate that the same receptor is present in the four species. OP(4) is expressed in neurons, where it reduces activation of adenylyl cyclase and Ca(2+) channels while activating K(+) channels in a manner similar to opioids. In this way, OP(4) mediates inhibitory effects in the autonomic nervous system, but its activities in the central nervous system can be either similar or opposite to those of opioids. In vivo experiments have demonstrated that NC modulates a variety of biological functions ranging from nociception to food intake, from memory processes to cardiovascular and renal functions, from spontaneous locomotor activity to gastrointestinal motility, from anxiety to the control of neurotransmitter release at peripheral and central sites. These actions have been demonstrated using NC and various pharmacological tools, as antisense oligonucleotides targeting OP(4) or the peptide precursor genes, antibodies against NC, an OP(4) receptor selective antagonist and with data obtained from animals in which the receptor or the peptide precursor genes were knocked out. These new advances have contributed to better understanding of the pathophysiological role of the NC/OP(4) system, and ultimately will help to identify the therapeutic potential of new OP(4) receptor ligands.|Amino Acid Sequence[MESH]|Animals[MESH]|Binding, Competitive[MESH]|Cardiovascular System/drug effects[MESH]|Humans[MESH]|Kidney/drug effects/physiology[MESH]|Molecular Sequence Data[MESH]|Motor Activity/drug effects[MESH]|Narcotic Antagonists[MESH]|Nociceptin[MESH]|Nociceptin Receptor[MESH]|Opioid Peptides/*pharmacology[MESH]|Receptors, Opioid/agonists/*metabolism[MESH] |
