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Regulatory Peptides and Cognate Receptors : Results and Problems in Cell Differentiation - Dietmar Richter

Regulatory Peptides and Cognate Receptors

Results and Problems in Cell Differentiation

By: Dietmar Richter (Editor)

Hardcover Published: 1999
ISBN: 9783540653257
Number Of Pages: 366

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In the last two decades, our knowledge on regulatory peptides and their cognate receptors, most of which are members of the seven transmembrane receptor families, has increased enormously. Regulatory peptides are small proteins which, besides their hormonal functions in regulating cellular metabolism in various tissues, may also act as neurotransmitters, and thus they often carry the prefix "neuro". Many of the cognate receptors involved in transducing the peptidergic signal across the cell membrane via a family of G proteins exist in multiple forms, the number of which frequently exceeds that of the corresponding peptide ligands. In this book, various peptide-receptor systems are discussed, e.g. CRF, somatostatin, TRH, opioid peptides, vasopressin, and oxytocin. It also discusses new strategies such as "reverse physiology" to uncover new peptides and orphan receptors.

The `Chicken and Egg? Problem of Co-evolution of Peptidesand Their Cognate Receptors: Which Came First?
Introductionp. 1
Appearance of Peptide Genes and Peptide Receptor Genesp. 2
Co-evolution of Peptide and Receptor Genesp. 2
Did Peptide Genes Arise Before Receptor Genes or Vice Versa?p. 3
Consequences of Genome Doubling During Vertebrate Evolutionp. 4
Multiple Receptors for a Given Peptide Ligandp. 4
Existence of Peptide Familiesp. 4
A Model for the Evolution of Specific Peptide-Receptor Interactionsp. 5
Possible Reasons for the Existence of Families of Receptors and Peptidesp. 6
Advantages of Having Multiple Receptors for a Given Peptidep. 7
Advantages of Having Multiple Peptides for a Given Receptorp. 8
Concluding Remarksp. 8
Referencesp. 9
Thyrotropin Releasing Hormone (TRH), the TRH-Receptorand the TRH-Degrading Ectoenzyme; Three Elementsof a Peptidergic Signalling System
Historical Backgroundp. 13
TRH, a Widespread and Multifunctional Signal Moleculep. 15
The Neuropeptide Hormone TRHp. 15
TRH, a Neuromodulator and/or Neurotransmitterp. 15
TRH in the Peripheryp. 16
Biosynthesis of TRHp. 17
Molecular Aspectsp. 17
Regulation of TRH Biosynthesisp. 20
TRH-Receptor and Signal Transductionp. 20
Molecular Aspects of the Pituitary TRH-Receptorp. 21
Regulation of the Pituitary TRH-Receptorp. 23
Inactivation of TRHp. 24
TRH-Metabolismp. 24
Characteristics of the TRH-Degrading Ectoenzyme (TRH-DE) and the TRH-Degrading Serum Enzymep. 25
Molecular Aspectsp. 25
The TRH-Degrading Serum Enzymep. 27
Hormonal Regulation of TRH-Inactivating Enzymesp. 27
Distribution of TRH, TRH-R and TRH-DE and Cellular Localizationp. 29
Future Aspectsp. 33
Referencesp. 35
Corticotropin-Releasing Factor (CRF)and its Role in the Central Nervous System
Introductionp. 43
Distribution of CRF and its mRNAp. 44
Distribution of CRF Receptors and Their mRNAsp. 45
CRF-Mediated Mechanisms in the Hypothalamus-Pituitary Systemp. 45
Role of Hypothalamic CRF Neurons in Stress Responses and Depressionp. 47
CRF Neurons in the Amygdala and Bed Nucleus of the Stria Terminalis, and Their Role in Fear and Anxietyp. 49
Locus Coeruleus and its Role in Stress Responses and Anxietyp. 52
CRF-Containing Climbing Fibers and Their Role in Cerebellar Functionsp. 54
Commentsp. 56
Referencesp. 59
CRF and CRF Receptors
Introductionp. 67
The CRF Family, a Chemical Considerationp. 67
Molecular Analysis of CRF Binding Sitesp. 70
Distribution of CRF-like Peptides and Their Binding Sites in the CNSp. 71
Distribution of CRF-like Peptides and Their Binding Sites in the Pituitaryp. 75
Immunomodulatory Effects of CRFp. 76
Neurotransmitter-like Actions of CRFp. 78
CRF and Cardiovascular Regulationp. 80
Role of the CRF System in Behaviorp. 81
Referencesp. 84
Neural Oxytocinergic Systems as Genomic Targets for Hormonesand as Modulators of Hormone-Dependent Behaviors
Behavioral Biology of Oxytocinp. 91
Hormonal Controls over Genes for Oxytocin and its Receptorp. 94
Means of Execution of Oxytocinergic Actionsp. 98
Oxytocin Mechanisms at the Cell Membrane Levelp. 98
Mechanisms at the Systems Levelp. 100
Summaryp. 101
Referencesp. 101
Vasopressin Receptors: Structural Functional Relationships and Role in Neural and Endocrine Regulation
Introductionp. 107
Physiological Functions of Vasopressin Systemsp. 108
Endocrine Functionsp. 108
Functions in the Brainp. 109
Paracrine Functionsp. 110
Vasopressin Receptor Distributionp. 111
Structural and Functional Relationships of Vasopressin Receptorsp. 117
Structurep. 117
Post-Translational Modificationsp. 121
Ligand Receptor Interactionsp. 122
G Protein-Couplingp. 124
V2 Receptor Mutations in Congenital Nephrogenic Diabetes Insipidusp. 125
Concluding Remarksp. 128
Referencesp. 128
The Oxytocin Receptor
Introductionp. 135
Pharmacology of the Oxytocin Receptor and its Signal Transductionp. 136
Extracellular N-Terminal Domainp. 137
Extracellular Loop Domainsp. 137
Transmembrane Domainsp. 139
Intracellular Loops, C-Terminus and Signal Transductionp. 140
Summaryp. 142
Expression of the Oxytocin Receptor in Vivo and its Functional Differentiationp. 142
The Uterus of Pregnancyp. 142
The Uterus of the Estrous Cyclep. 147
The Cervixp. 148
The M ammary Glandp. 149
The Ovaryp. 150
The Brainp. 150
The Kidneyp. 151
The Male Reproductive Systemp. 151
Oxytocin-Responsive Cell-Linesp. 152
Regulation of Oxytocin Receptor Expressionp. 153
Structure and Regulation of the OTR Genep. 155
General Conclusionsp. 159
Referencesp. 160
Targeted Mutagenesis of the Murine Opioid System
Introductionp. 169
A Brief History of the Opioid Systemp. 169
Techniques in Murine Mutagenesisp. 171
Gene Deletion Studies in the Opioid Systemp. 172
Stress-Induced Analgesiap. 173
Nociceptionp. 174
Opioid Pharmacology of Opioid System Knock-out Micep. 176
Receptor Pharmacology in the Receptor Knock-out Micep. 176
and Pharmacology in the Receptor Knock-out Micep. 177
Pharmacology in the and Receptor Knock-out Micep. 178
Opioid Pharmacology in the ß-Endorphin Knock-out Micep. 178
Behavioral Reinforcement and Rewardp. 180
Genetic Background of Mutant Micep. 181
Differences Between Knock-out Linesp. 183
Construct Differences Between Receptor Knock-out Mice Linesp. 183
Genetic Differences Between Background Strains Used for Producing Mutant Micep. 184
Conclusionsp. 185
Referencesp. 186
Orphan Receptors and the Concept of Reverse Physiology: Discovery of the Novel Neuropeptide Orphanin FQ/Nociceptin
Summaryp. 193
Orphan Receptors and the Concept of Reverse Physiologyp. 194
Identification of the Natural Ligand of an Orphan GPCR: Orphanin FQ/Nociceptinp. 195
Evidence for OFQ/NOC being a Neurotransmitterp. 196
Receptor Binding of OFQ/NOCp. 196
Cellular Responses to OFQ/NOCp. 197
Biosynthesis, Degradation and Release of OFQ/NOCp. 197
Regional Expression of OFQ/NOC and its Receptorp. 199
Physiological Effects and Behavioral Responses of OFQ/NOCp. 200
Similarities and Differences Between the Opioid and the OFQ/NOC Systemsp. 204
Novel Peptides Derived from the OFQ/NOC Precursorp. 206
Conclusions: The Strength and the Pitfalls of the Orphan Receptor Strategyp. 207
Referencesp. 209
Molecular Biology of the Receptors for Somatostatin and Cortistatin
Introductionp. 215
The Peptidesp. 215
Clinical Aspectsp. 217
Somatostatin Receptorsp. 218
The Regulation of SSTR Gene Expressionp. 221
Signal Transduction Through Somatostatin Receptor Subtypesp. 222
Do we Need Even More Receptor Subtypes?p. 225
Subtype Specific Differences in Receptor Regulation and Intracellular Distributionp. 225
Towards an Understanding of the Functional Role of Individual Somatostatin Receptor Subtypesp. 229
Conclusionp. 231
Referencesp. 231
Novel Neurotransmitters for Sleep and Energy Homeostasis
Summaryp. 239
Introductionp. 240
Cortistatinp. 240
A Novel Somatostatin-Like Neuropeptidep. 240
Cortistatin in Cortical Interneuronsp. 241
Partial Coexpression with Somatostatin, Parvalbumin and Calbindinp. 242
Late Onset and Transient Expressionp. 243
Binding to Somatostatin Receptorsp. 243
Neuronal Depressant Activityp. 244
Cortistatin Has Sleep-Promoting Propertiesp. 245
Cortistatin Antagonizes Acetylcholinep. 245
Cortistatin: A Pressure for Sleepp. 247
Cortistatin: Not an Alternative Somatostatinp. 247
The Hypocretins (Orexins)p. 248
Two Hypothalamus-Specific Peptidesp. 248
Hypocretin in Cell Bodies, Fibers and Synaptic Vesiclesp. 250
Hcrt2 Is Neuroexcitatoryp. 251
Endogenous Peptides and Their Receptorsp. 251
A Role in Feedingp. 252
Hypocretins in Many Physiological Systemsp. 252
Peptides as Pressures for Voluntary but Necessary Behaviorsp. 253
Referencesp. 254
Galanin and Galanin Receptors
Introductionp. 257
Galaninp. 258
Peptide Sequencep. 258
Preprogalanin Gene Structure and Chromosomal Localisationp. 260
Sites and Regulation of Galanin Expressionp. 262
Developmental Expression and Sexual Dimorphismp. 262
Transcriptional Regulationp. 262
Galanin Receptorsp. 263
Cloning, Pharmacology, Signalling Properties and Sites of Expressionp. 264
GALR1p. 264
GALR2p. 265
GALR3p. 267
Other Galanin Binding Sitesp. 268
Galanin Receptor Gene Structurep. 271
Chromosomal Localisation of Galanin Receptor Genesp. 272
Physiological Effects and Therapeutic Indicationsp. 273
Learning, Memory and Cognitionp. 273
Feeding Behaviour and Obesityp. 274
Neuroendocrine Responsesp. 275
Analgesia and Neuropathic Painp. 277
Nerve Injury and Regenerationp. 278
Mitogenesis: Development and Tumourigenesisp. 279
Summary and Conclusionsp. 280
Referencesp. 280
The Cholecystokinin - Gastrin Family of Peptides and Their Receptors
Introductionp. 293
Structure-Function Relationshipsp. 294
Gastrin and Cholecystokinin Genes and mRNAsp. 299
Progastrin Maturationp. 302
Procholecystokinin Maturationp. 306
Gastrin and Cholecystokinin Receptorsp. 309
Summary and Perspectivep. 312
Referencesp. 313
Function of the Neuropeptide Head Activator for Early Neuraland Neuroendocrine Development
Introductionp. 323
Action of HA as Morphogen in Hydrap. 323
HA Signal Transduction to Initiate Mitosisp. 324
Corelease of HA with a Carrier Complexp. 326
HA Binding Proteinp. 327
HAB Expression in Mouse Developmentp. 330
HAB Functionp. 334
Referencesp. 335
Invertebrate Neurohormones and Their Receptors
Introductionp. 339
Cnidariansp. 339
Neurohormones in Cnidariansp. 340
Biosynthesis of Neurohormones in Cnidariansp. 343
Neurohormone Receptors in Cnidariansp. 349
Neurohormone Receptors in Insectsp. 351
Conclusionp. 358
Referencesp. 358
Subject Indexp. 363
Table of Contents provided by Publisher. All Rights Reserved.

ISBN: 9783540653257
ISBN-10: 3540653252
Series: Results and Problems in Cell Differentiation
Audience: Professional
Format: Hardcover
Language: English
Number Of Pages: 366
Published: 1999
Publisher: Springer-Verlag Berlin and Heidelberg Gmbh & Co. Kg
Country of Publication: DE
Dimensions (cm): 23.5 x 15.5  x 2.54
Weight (kg): 0.81