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Table of Contents
Intro; Preface; Contents; The History of N/OFQ and the NOP Receptor; 1 Introduction; 2 The ``Orphan Receptor Strategy ́́Launches the Era of ``Reverse Pharmacology;́́ 3 The Quest for the Endogenous Ligand of ORL1 (and Other Orphan GPCRs); 3.1 Uncertainties Setting the Stage; 3.2 In the Eye of the Storm: It Is Back to cAMP; 3.3 The Isolation; 4 The Novel Opioid Peptide from Basel...; 5 ... Is Simultaneously Discovered in Toulouse; 6 Race to the Finish Line; 7 Early Steps to Uncover the Physiological Functions of N/OFQ; 8 Hopes for Clinical Applications; 9 Reverse Pharmacology Success Stories
10 ConclusionReferences; NOP-Targeted Peptide Ligands; 1 Introduction; 2 Structure-Activity Relationship Studies on N/OFQ-Related Peptides; 2.1 Linear N/OFQ Derivatives; 2.2 Cyclic N/OFQ Derivatives; 3 Structure-Activity Relationship Studies on N/OFQ-Unrelated Peptides; 4 Bivalent NOP Peptide Ligands; 5 Tetrabranched NOP Peptide Ligands; 6 Concluding Remarks; References; NOP-Targeted Nonpeptide Ligands; 1 Nonpeptide NOP Ligands As Tools and Candidate Drugs in Development; 2 Structure-Activity, Structure-Selectivity, and Structure-Function Relationships of Nonpeptide NOP Ligands
2.1 G-Protein-Activated Inwardly Rectifying K+ Channels (Kir3)2.1.1 The Periaqueductal Grey; 2.1.2 The Rostral Ventral Medial Medulla; 2.1.3 The Amygdala; 2.1.4 The Locus Coeruleus; 2.1.5 The Dorsal Raphe Nucleus; 2.1.6 The Spinal Cord; 2.2 Voltage-Gated Calcium Channels (CaV); 2.2.1 Primary Sensory Neurons; 2.2.2 CNS Neurons; 2.3 Other Postsynaptic N/OFQ Actions; 2.4 NOP Desensitisation; 3 Presynaptic Actions of N/OFQ; 3.1 Short-Term Modulation of Neurotransmitter Release; 3.1.1 Locus of Action: Presynaptic; 3.1.2 Mechanisms of Presynaptic Action; 3.2 Long-Term Synaptic Plasticity
4 Implications of the Electrophysiological Actions of N/OFQ in NociceptionReferences; NOP Receptor Signaling Cascades; 1 Classic Gi-Signaling Pathways; 2 NOP Receptors and Kinase Signaling; 3 NOP Receptors and Arrestin Signaling; 4 Conclusion; References; Regulation of the Genes Encoding the ppN/OFQ and NOP Receptor; 1 Nociceptin/Orphanin FQ (N/OFQ): Gene, Transcriptional Regulation, and Neuropeptide Precursor; 2 NOP Receptor: Gene and Transcriptional Regulation; 3 Genetic Manipulation of the N/OFQ-NOP Receptor System; 4 ppN/OFQ and NOP Receptor Gene Polymorphisms
10 ConclusionReferences; NOP-Targeted Peptide Ligands; 1 Introduction; 2 Structure-Activity Relationship Studies on N/OFQ-Related Peptides; 2.1 Linear N/OFQ Derivatives; 2.2 Cyclic N/OFQ Derivatives; 3 Structure-Activity Relationship Studies on N/OFQ-Unrelated Peptides; 4 Bivalent NOP Peptide Ligands; 5 Tetrabranched NOP Peptide Ligands; 6 Concluding Remarks; References; NOP-Targeted Nonpeptide Ligands; 1 Nonpeptide NOP Ligands As Tools and Candidate Drugs in Development; 2 Structure-Activity, Structure-Selectivity, and Structure-Function Relationships of Nonpeptide NOP Ligands
2.1 G-Protein-Activated Inwardly Rectifying K+ Channels (Kir3)2.1.1 The Periaqueductal Grey; 2.1.2 The Rostral Ventral Medial Medulla; 2.1.3 The Amygdala; 2.1.4 The Locus Coeruleus; 2.1.5 The Dorsal Raphe Nucleus; 2.1.6 The Spinal Cord; 2.2 Voltage-Gated Calcium Channels (CaV); 2.2.1 Primary Sensory Neurons; 2.2.2 CNS Neurons; 2.3 Other Postsynaptic N/OFQ Actions; 2.4 NOP Desensitisation; 3 Presynaptic Actions of N/OFQ; 3.1 Short-Term Modulation of Neurotransmitter Release; 3.1.1 Locus of Action: Presynaptic; 3.1.2 Mechanisms of Presynaptic Action; 3.2 Long-Term Synaptic Plasticity
4 Implications of the Electrophysiological Actions of N/OFQ in NociceptionReferences; NOP Receptor Signaling Cascades; 1 Classic Gi-Signaling Pathways; 2 NOP Receptors and Kinase Signaling; 3 NOP Receptors and Arrestin Signaling; 4 Conclusion; References; Regulation of the Genes Encoding the ppN/OFQ and NOP Receptor; 1 Nociceptin/Orphanin FQ (N/OFQ): Gene, Transcriptional Regulation, and Neuropeptide Precursor; 2 NOP Receptor: Gene and Transcriptional Regulation; 3 Genetic Manipulation of the N/OFQ-NOP Receptor System; 4 ppN/OFQ and NOP Receptor Gene Polymorphisms