Litwack Nociceptin Opioid

1. Auflage 2015
ISBN: 978-0-12-802593-2
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, Band Volume 97, 358 Seiten

Reihe: Vitamins and Hormones

First published in 1943, Vitamins and Hormones is the longest-running serial published by Academic Press. The Series provides up-to-date information on vitamin and hormone research spanning data from molecular biology to the clinic. A volume can focus on a single molecule or on a disease that is related to vitamins or hormones. A hormone is interpreted broadly so that related substances, such as transmitters, cytokines, growth factors and others can be reviewed. This volume focuses on nociceptin opioid. - Expertise of the contributors - Coverage of a vast array of subjects - In depth current information at the molecular to the clinical levels - Three-dimensional structures in color - Elaborate signaling pathways

Autoren/Hrsg.

Litwack, Gerald

Inhaltsverzeichnis

1;Front Cover;1
2;Nociceptin Opioid;4
3;Copyright;5
4;Contents;8
5;Contributors;12
6;Preface;16
7;Chapter 1: Helix-Constrained Nociceptin Peptides Are Potent Agonists and Antagonists of ORL-1 and Nociception;18
7.1;1. Nociception in Brief;19
7.1.1;1.1. Opioid receptor-like receptor—ORL-1;21
7.1.2;1.2. Nociceptin;24
7.1.3;1.3. Interrogating the activation and address domains of nociceptin(1-17);26
7.2;2. Prospecting the Importance of the N-Terminal Tetrapeptide of Nociceptin(1-17);28
7.3;3. Other Modifications to Nociceptin(1-17);30
7.4;4. The Importance of Structure in Nociceptin Analogues;32
7.4.1;4.1. Importance of helicity;32
7.4.2;4.2. Other nociceptin derivatives;33
7.5;5. Recent Advances in ORL-1 Active Nociceptin Peptides;34
7.6;6. The Development of New Helix-Constrained Nociceptin Analogues;35
7.6.1;6.1. Design of helix-constrained nociceptin analogues;35
7.6.2;6.2. Helical structure of nociceptin(1-17)-NH2 analogues in water;36
7.6.3;6.3. Nuclear magnetic resonance spectra-derived structures;39
7.7;7. Biological Properties of Helical Nociceptin Mimetics;45
7.7.1;7.1. Cellular expression of ORL-1 and ERK phosphorylation;45
7.7.2;7.2. Agonist and antagonist activity of nociceptin(1-17)-NH2 and analogues;51
7.7.3;7.3. Effects of helical constraint on biological activity in Neuro-2a cells;57
7.7.4;7.4. Stability and cell toxicity of helix-constrained versus unconstrained peptides;60
7.7.5;7.5. In vivo activity of helix-constrained versus unconstrained nociceptin analogues;61
7.8;8. Concluding Remarks;63
7.9;References;63
8;Chapter 2: Bioinformatics and Evolution of Vertebrate Nociceptin and Opioid Receptors;74
8.1;1. Introduction;75
8.1.1;1.1. The origin of G protein-coupled receptors;76
8.1.2;1.2. A brief history of opioid receptors;77
8.1.3;1.3. Evidence for opioid receptors in nonmammalian vertebrates;80
8.2;2. The Vertebrate Opioid Receptor Sequence Database;82
8.2.1;2.1. Alignment of protein sequences;83
8.2.2;2.2. Phylogenetic analysis of vertebrate opioid receptors;86
8.2.3;2.3. Divergence and convergence of opioid receptor types;88
8.3;3. The Human Genome and the Evolution of Opioid Receptors;91
8.3.1;3.1. Duplicated opioid family receptor genes in the human genome;91
8.3.2;3.2. Variation in human opioid receptor genes;92
8.4;4. The Molecular Evolution of Vertebrate Opioid Family Receptors;96
8.5;5. Future Directions;98
8.6;6. Conclusions;100
8.7;Acknowledgments;101
8.8;References;101
9;Chapter 3: Ancestral Vertebrate Complexity of the Opioid System;112
9.1;1. Introduction;113
9.2;2. Opioid Peptide Family;117
9.3;3. Opioid Receptor Family;122
9.4;4. Discussion: Complexity, Coevolution, and Divergence;130
9.5;5. Conclusions;135
9.6;Acknowledgement;135
9.7;References;135
10;Chapter 4: Synthesis and Biological Activity of Small Peptides as NOP and Opioid Receptors' Ligands: View on Current Devel...;140
10.1;1. Introduction;141
10.2;2. Endogenous Opioid Peptides and Receptors: Nociceptin and NOP Receptor Ligands;143
10.3;3. Hexapeptides with NOP Receptor Affinity;150
10.4;4. Solid-Phase Peptide Synthesis;153
10.5;5. Conclusions;158
10.6;Acknowledgment;158
10.7;References;158
11;Chapter 5: Pain Regulation by Nocistatin-Targeting Molecules: G Protein-Coupled-Receptor and Nocistatin-Interacting Protein;164
11.1;1. Introduction;165
11.2;2. Biological Activity by NST Through G Protein-Coupled Receptor;169
11.2.1;2.1. Regulation of presynaptic neurotransmitter release through putative Gi/o-coupled NST receptor;169
11.2.2;2.2. Regulation of postsynaptic transmission through putative Gi/o-coupled NST receptor;170
11.2.3;2.3. Depolarization of projection neurons by a putative Gq/11-coupled NST receptor;171
11.3;3. Pain Regulation Through an NST-Interacting Protein;172
11.3.1;3.1. Purification of an NST-interacting protein using high-performance affinity latex nanobeads;172
11.3.2;3.2. Identification of NIPSNAP1 as an NST-interacting protein;173
11.3.3;3.3. Pain regulation induced by NIPSNAP1;174
11.3.4;3.4. Other functions of NIPSNAP1;176
11.4;4. Conclusions;177
11.5;Acknowledgment;178
11.6;References;178
12;Chapter 6: Nociceptin and Meiosis during Spermatogenesis in Postnatal Testes;184
12.1;1. Introduction;185
12.1.1;1.1. Meiotic chromosome dynamics during spermatogenesis;185
12.1.2;1.2. A role in spermatogenesis of FSH and the mechanism of its action;186
12.2;2. Regulation of Nociceptin Expression by FSH Signaling in Sertoli Cells;187
12.2.1;2.1. Phosphorylation of CREB following cAMP stimulation in a Sertoli cell line;187
12.2.2;2.2. Identification of prepronociceptin gene associating cAMP-dependently with phosphorylated CREB;189
12.2.3;2.3. Effects of cAMP and FSH on the expressions of prepronociceptin mRNA and the nociceptin peptide in Sertoli cells and ...;189
12.2.4;2.4. Expression of the endogenous nociceptin peptide in testes;190
12.3;3. Function of Nociceptin During Meiosis in Spermatocytes;190
12.3.1;3.1. The expression of endogenous Oprl-1 and the phosphorylation of endogenous Rec8 in testes;190
12.3.2;3.2. Effect of nociceptin on the phosphorylation of Rec8 in testes;191
12.3.3;3.3. Effect of nociceptin on the progress of meiosis during spermatogenesis;193
12.3.4;3.4. Effect of FSH on the phosphorylation of Rec8 in testes;194
12.4;4. Nociceptin is a Novel Paracrine Factor that is Induced in Sertoli Cells and Mediates to Germ Cells the Effect of FSH o...;195
12.4.1;4.1. Prepronociceptin gene is transcriptionally regulated by FSH signaling in Sertoli cells;195
12.4.2;4.2. Nociceptin is a paracrine factor mediating the FSH-regulated germ cell development;196
12.5;5. Nociceptin is a Novel Extrinsic Factor Inducing Rec8 Phosphorylation and Chromosome Dynamics During Meiosis in Spermat...;198
12.5.1;5.1. Nociceptin is an extrinsic regulator for Rec8 phosphorylation during meiosis in spermatocytes;198
12.5.2;5.2. Nociceptin is a testicular peptide, "testipeptide," that is expressed and functions locally within testes;200
12.6;6. Conclusions;200
12.7;Acknowledgments;201
12.8;References;201
13;Chapter 7: Orphanin FQ-ORL-1 Regulation of Reproduction and Reproductive Behavior in the Female;204
13.1;1. Introduction;206
13.2;2. Ovarian Hormone Regulation of Reproductive Behavior and Neuroendocrine Feedback Loops;207
13.2.1;2.1. Neuroendocrine feedback loops;207
13.2.2;2.2. Reproductive behavior;208
13.3;3. OFQ/N-ORL-1 Regulation of Sexual Receptivity;214
13.4;4. Ovarian Steroid Regulation of OFQ/N and ORL-1 Expression and Signaling;219
13.5;5. OFQ/N-ORL-1 Regulation of GnRH and LH Release During Positive and Negative Feedback;223
13.6;6. Conclusions;226
13.7;Acknowledgments;226
13.8;References;227
14;Chapter 8: Effects of Nociceptin and Nocistatin on Uterine Contraction;240
14.1;1. Roles of PNOC, N/OFQ, and NST in Different Peripheral Tissues;241
14.1.1;1.1. White blood cells;241
14.1.2;1.2. Airways;242
14.1.3;1.3. Liver;242
14.1.4;1.4. Skin;242
14.1.5;1.5. Vascular smooth muscle;243
14.1.6;1.6. Intestinal smooth muscle;243
14.1.7;1.7. Ovary;243
14.1.8;1.8. Testis;244
14.2;2. Presence of PNOC, N/OFQ, and NST in Uterine Tissue;244
14.2.1;2.1. PNOC in the uterus;245
14.2.2;2.2. N/OFQ and NST in the uterus;246
14.3;3. The Effects and Mechanisms of Action of N/OFQ and NST on Uterine Contractility;248
14.3.1;3.1. The effect of N/OFQ on uterine contractility;248
14.3.2;3.2. The effect of NST on uterine contractility;250
14.3.3;3.3. The combined effect of N/OFQ and NST on uterine contractility;252
14.4;4. Conclusions;252
14.5;References;254
15;Chapter 9: Nociceptin/Orphanin FQ-NOP Receptor System in Inflammatory and Immune-Mediated Diseases;258
15.1;1. A Brief Overview of the Immune Response;259
15.2;2. N/OFQ and Its Receptor;261
15.3;3. N/OFQ and NOP Receptor Expression in Leukocytes;262
15.4;4. Effects of NOP Receptor Activation on the Immune Response;262
15.5;5. NOP Receptor Activation and Inflammatory and Autoimmune Diseases;267
15.6;6. Molecular Mechanisms Underlying N/OFQ Actions on Immune Functions;272
15.7;7. Relationship Between N/OFQ, Stress, and HPA Axis;273
15.8;8. Conclusions;276
15.9;Acknowledgments;276
15.10;References;276
16;Chapter 10: Endogenous Nociceptin System Involvement in Stress Responses and Anxiety Behavior;284
16.1;1. Introduction;285
16.1.1;1.1. Nociceptin peptide and receptor system;285
16.1.2;1.2. Nociceptin and NOP receptor: Relevance to inflammation;286
16.1.3;1.3. Nociceptin and NOP receptor: Relevance to anxiety and stress;288
16.2;2. The Neuroanatomical Basis of Fear Conditioning;292
16.3;3. Evidence for a Role of Nociceptin in Fear Learning and Memory;293
16.4;4. Nociceptin and Neurochemical Substrates of Fear Conditioning: Focus on Biogenic Amines;294
16.5;5. Maternal Adaptations of the Nociceptin System;296
16.5.1;5.1. Maternal adaptations in neuroendocrine behavioral and stress responses;297
16.5.2;5.2. Prepartum adaptations and changes in N/OFQ expression and function;298
16.6;6. Conclusions;300
16.7;References;300
17;Chapter 11: The Neuronal Circuit Between Nociceptin/Orphanin FQ and Hypocretins/Orexins Coordinately Modulates Stress-Ind...;312
17.1;1. Introduction;313
17.2;2. The N/OFQ System;314
17.2.1;2.1. The discovery of N/OFQ;314
17.2.2;2.2. Complex modulation of nociceptive processing by N/OFQ;315
17.2.3;2.3. N/OFQ and the stress response;316
17.3;3. The Hypocretins/Orexins System;317
17.3.1;3.1. The discovery of Hcrts;317
17.3.2;3.2. Hcrt-induced analgesia;318
17.3.3;3.3. Hcrts and stress responses;319
17.4;4. Interaction Between the N/OFQ and Hcrt Systems;320
17.4.1;4.1. A local and direct neuronal circuit between N/OFQ- and Hcrt-producing neurons;321
17.4.2;4.2. Cellular physiological and pharmacological actions of N/OFQ on Hcrt neurons;323
17.4.3;4.3. Coordinated modulation of SIA;325
17.4.4;4.4. Coordinated modulation of anxiety-related behavior;328
17.5;5. Conclusions;330
17.6;Acknowledgments;333
17.7;References;333
18;Chapter 12: Nociceptin/Orphanin-FQ Modulation of Learning and Memory;340
18.1;1. Introduction;340
18.2;2. N/OFQ Modulation of Mnemonic Functions;342
18.2.1;2.1. N/OFQ modulation of spatial learning;342
18.2.2;2.2. N/OFQ modulation of fear learning and memory;346
18.2.2.1;2.2.1. Fear conditioning learning;347
18.2.2.2;2.2.2. Passive avoidance learning;349
18.2.3;2.3. N/OFQ modulation of recognition memory;351
18.2.4;2.4. N/OFQ modulation of working memory;352
18.2.5;2.5. N/OFQ modulation of sensorimotor gating;354
18.3;3. Mechanisms of N/OFQ-Mediated Modulation of Cognitive Functions;355
18.4;4. Conclusion and Remarks;357
18.5;Acknowledgments;358
18.6;References;358
19;Index;364
20;Color Plate;375

Leseproben

Chapter One Helix-Constrained Nociceptin Peptides Are Potent Agonists and Antagonists of ORL-1 and Nociception
Rink-Jan Lohman1; Rosemary S. Harrison1; Gloria Ruiz-Gómez; Huy N. Hoang; Nicholas E. Shepherd; Shiao Chow; Timothy A. Hill; Praveen K. Madala; David P. Fairlie2    Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia
2 Corresponding author: email address: [e-mail]
1 Joint first authors Abstract
Nociceptin (orphanin FQ) is a 17-residue neuropeptide hormone with roles in both nociception and analgesia. It is an opioid-like peptide that binds to and activates the G-protein-coupled receptor opioid receptor-like-1 (ORL-1, NOP, orphanin FQ receptor, kappa-type 3 opioid receptor) on central and peripheral nervous tissue, without activating classic delta-, kappa-, or mu-opioid receptors or being inhibited by the classic opioid antagonist naloxone. The three-dimensional structure of ORL-1 was recently published, and the activation mechanism is believed to involve capture by ORL-1 of the high-affinity binding, prohelical C-terminus. This likely anchors the receptor-activating N-terminus of nociception nearby for insertion in the membrane-spanning helices of ORL-1. In search of higher agonist potency, two lysine and two aspartate residues were strategically incorporated into the receptor-binding C-terminus of the nociceptin sequence and two Lys(i) ? Asp(i + 4) side chain–side chain condensations were used to generate lactam cross-links that constrained nociceptin into a highly stable a-helix in water. A cell-based assay was developed using natively expressed ORL-1 receptors on mouse neuroblastoma cells to measure phosphorylated ERK as a reporter of agonist-induced receptor activation and intracellular signaling. Agonist activity was increased up to 20-fold over native nociceptin using a combination of this helix-inducing strategy and other amino acid modifications. An NMR-derived three-dimensional solution structure is described for a potent ORL-1 agonist derived from nociceptin, along with structure–activity relationships leading to the most potent known a-helical ORL-1 agonist (EC50 40 pM, pERK, Neuro-2a cells) and antagonist (IC50 7 nM, pERK, Neuro-2a cells). These a-helix-constrained mimetics of nociceptin(1–17) had enhanced serum stability relative to unconstrained peptide analogues and nociceptin itself, were not cytotoxic, and displayed potent thermal analgesic and antianalgesic properties in rats (ED50 70 pmol, IC50 10 nmol, s.c.), suggesting promising uses in vivo for the treatment of pain and other ORL-1-mediated responses. Keywords Nociceptin Nociception Analgesia ORL Agonist Helix 1 Nociception in Brief
Nociception is a term used to describe the ability of organisms to detect noxious stimuli (Wall & Melzack, 2000). It involves neural processing of external stimuli, signaling through receptors on neurons, that may damage the organism, enabling it to sense pain and take action to evade damage. In higher organisms, nociception is a series of exquisitely complex neural events involving neurons of the peripheral and central nervous system (CNS) that allow an organism to sense pain or algesia (Wall & Melzack, 2000). Noxious stimuli can be mechanical (pressure or sharp objects), thermal (temperatures above 45 °C or extreme cold), and chemical (acids, environmental irritants such as capsaicin), which are detected by an array of specialized receptors (termed nociceptors) on the terminals of spinal nerve afferents that have their cell bodies in ganglia positioned outside of the spinal cord. These pain-sensing neurons (canonically unmyelinated, slow conduction velocity C-fibers and myelinated moderate conduction velocity Ad-fibers) are generally considered part of the peripheral nervous system and send signals after detection of noxious stimuli via their extraspinal ganglia to the dorsal horn of the spinal cord en route to the brain for processing of conscious pain perception (Wall & Melzack, 2000). This ultimately allows the organism to act to avoid further damage by removing itself from the noxious stimuli or cause tissue injury, and allow healing. To add to the complexity, the initial response to pain avoidance is usually considered a reflex action, with the withdrawal response not initially involving the brain (Wall & Melzack, 2000). Aside from the classical descriptions of pain in uninjured tissue via specialized nociceptors globally referred to as mechanoceptors, thermoceptors, and chemoceptors (with obvious nomenclature), pain can be promoted by endogenous inflammatory mediators released from various inflammatory cells (Wall & Melzack, 2000). These mediators are detected by diverse classes of chemoceptors that respond to many exogenous and endogenous chemicals, including histamine (Harasawa, 2000; Rosa & Fantozzi, 2013) (H1 receptors: Akdis & Simons, 2006; possibly others, H2: Hasanein, 2011; Mobarakeh et al., 2005; and H3: Cannon & Hough, 2005; Smith, Haskelberg, Tracey, & Moalem-Taylor, 2007), neuropeptides (Abrams & Recht, 1982) such as substance P (Munoz & Covenas, 2011), enkephalins (Bodnar, 2013), and bradykinins (Jaggi & Singh, 2011; Maurer et al., 2011) via various receptors including the NK1 and transient receptor potential channel families (Brederson, Kym, & Szallasi, 2013; Salat, Moniczewski, & Librowski, 2013). Even various proteases (such as tryptase) acting at protease-activated receptors (Bao, Hou, & Hua, 2014; Bunnett, 2006; Vergnolle et al., 2001) can signal pain. These substances via their receptors can contribute to a heightened pain sensation, referred to as hyperalgesia, which describes when a normally painful stimulus becomes excessively painful. However, if persistent it can lead to allodynia, when a normally nonpainful stimulus becomes painful to the individual (Wall & Melzack, 2000). These can both be symptoms of normal inflammatory pain and can be of benefit to an organism by warning the individual of tissue damage. However, when pain becomes chronic, it can seriously interfere with the quality of life of the individual, leading to significant morbidity. Such pain is considered neuropathic if it becomes either ongoing or episodic in nature, the cause of which may be in absence of a known or precipitating inflammatory condition or lesion. Such chronic pain is commonly treated with opiates, a name given to a family of alkaloids, such as morphine or codeine, derived from the opium poppy (Papaver somniferum), or their synthetic counterparts, the opioids, all of which act through G-protein-coupled receptors of the opioid receptor family (delta (d1–2), kappa (?1–3), and mu (µ1–3); Wall & Melzack, 2000). However, the actions of the opiate alkaloids at their receptors can produce significant and unwanted effects such as respiratory depression, physical dependence, sedation, hallucinations, and other dissociative effects that may significantly impact on an individual's well-being and contribution to society if taken for extended periods, as generally required for chronic pain sufferers. Likewise, once they are no longer needed due to resolution of the condition, withdrawal symptoms precipitated by their dependence effects may result, and these are not only unpleasant, but can be devastating to patients and their families if dependence becomes abuse. This limits their effectiveness as drugs for the greater population, and thus there is a requirement for potent antinociceptive compounds that target the opioid receptors without the side effects of the classical alkaloid opiates. 1.1 Opioid receptor-like receptor—ORL-1
A relatively recent addition to the GPCR opioid receptor family is the opioid receptor-like-1 (ORL-1 or NOP) receptor (Fig. 1). It was named because of high homology with the classical opioid receptors, but it was not affected by classical opioid receptor antagonists such as naloxone. The “orphan” receptor ORL-1 was initially identified from mRNA transcripts taken from mouse and rat CNSs, and deorphanized with the discovery of nociceptin as an endogenous ligand (Bunzow et al., 1994; Chen et al., 1994; Meunier et al., 1995; Mollereau et al., 1994; Salvadori, Guerrini, Calo, & Regoli, 1999; Wang et al., 1994; Wick, Minnerath, Roy, Ramakrishnan, & Loh, 1995). The location of the ORL-1 receptor has since been confirmed, and receptor-binding assays and in situ hybridization techniques have been used to pinpoint ORL-1 to the cortex, anterior olfactory nucleus, lateral septum, hypothalamus, hippocampus, amygdala, and other regions of the brain. Interestingly, ORL-1 transcripts have also been identified in nonneuronal peripheral organs such as intestine, vas deferens, kidney, and the spleen (Osinski, Pampusch, Murtaugh, & Brown, 1999; Wang et al., 1994) and in unexpected cell types, such as mouse sphenic lymphocytes (Halford, Gebhardt, & Carr, 1995) as...