Linden Pharmacology of Purine and Pyrimidine Receptors

1. Auflage 2011
ISBN: 978-0-12-385533-6
Verlag: Elsevier Science & Techn.
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, Band Volume 61, 558 Seiten, Web PDF

Reihe: Advances in Pharmacology

This is an overview of the fast-moving field of purinergic signalling through adenosine and ATP receptors. - Authors are the leading authorities in their fields - Subject matter is important for understanding tissue protection - Subject matter is of intense interest for new drug development

Autoren/Hrsg.

Linden, Joel

Inhaltsverzeichnis

1;Front Cover;1
2;Pharmacology of Purineand Pyrimidine Receptors;4
3;Copyright;5
4;Contents;6
5;Contributors;12
6;Preface;16
6.1;References;17
7;Chapter 1: The Structure of the Adenosine Receptors;18
7.1;I. Introduction;18
7.2;II. Primary Sequence and Covalent Modifications of the Adenosine A2A Receptors;20
7.3;III. The A2AAR Crystal Structure;22
7.4;IV. Binding Selectivity Across the ARs;40
7.5;V. Receptor Structure and Receptor Homology Modeling;43
7.6;VI. In Silico Screening;46
7.7;VII. Conclusion;49
7.8;References;51
8;Chapter 2: Adenosine Receptors in Health and Disease;58
8.1;I. Introduction;58
8.2;II. A1 Adenosine Receptors;60
8.3;III. A2A Adenosine Receptors;64
8.4;IV. A2B Adenosine Receptors;69
8.5;V. A3 Adenosine Receptors;73
8.6;VI. Conclusion;79
8.7;References;82
9;Chapter 3: Adenosine and the Regulation of Metabolism and Body Temperature;94
9.1;I. Introduction. The Concept of Adenosine as an Emergency Signal;94
9.2;II. Adenosine and the Regulation of Lipid Metabolism;96
9.3;III. Adenosine and Glucose Homeostasis;99
9.4;IV. Central Regulation of Metabolism, Sleep, and Wakefulness;101
9.5;V. Regulation of Temperature;103
9.6;VI. Conclusion;105
9.7;Acknowledgments;106
9.8;References;106
10;Chapter 4: Regulation of Leukocyte Function by Adenosine Receptors;112
10.1;I. Introduction;113
10.2;II. Immune Responses to Adenosine Receptor Signaling;114
10.3;III. Disease Relevance of Adenosine to Immune Signaling;121
10.4;IV. Conclusion;123
10.5;Disclosure Statement;124
10.6;References;124
11;Chapter 5: Receptors in Inflammation;132
11.1;I. Introduction;132
11.2;II. Tools to Study A2B Adenosine Receptor Function;133
11.3;III. A2B Receptors on Immune Cells;134
11.4;IV. A2B Receptors on Endothelial Cells;140
11.5;V. A2B Receptors on Epithelial Cells;144
11.6;VI. Role of A2B Receptors on Fibroblasts;147
11.7;VII. Role of A2B Receptors in Animal Models of Inflammation;148
11.8;VIII. Conclusions;151
11.9;Acknowledgments;152
11.10;References;153
12;Chapter 6: Adenosine Receptors in Tissue Protection;162
12.1;I. Introduction;163
12.2;II. Relationship Between Hypoxia and Inflammation;165
12.3;III. Effect of Hypoxia on the Extracellular Availability of Adenosine;173
12.4;IV. Alteration of ADORA2B Signaling by Hypoxia;179
12.5;V. Examples of ADORA2B Signaling in Tissue Protection from Hypoxia;180
12.6;VI. Other ARs than the ADORA2B During Hypoxia;188
12.7;VII. Conclusion;188
12.8;Acknowledgment;189
12.9;References;190
13;Chapter 7: Allosteric Modulation of Purine and Pyrimidine Receptors;204
13.1;I. Introduction;205
13.2;II. AR Modulators;207
13.3;III. "Translational" Assessment of a Prototypical PAM of A1 AR;218
13.4;IV. Allosteric Modulators of P2Y and P2X Receptors for Nucleotides;225
13.5;V. Conclusion;228
13.6;Acknowledgments;228
13.7;References;230
14;Chapter 8: Molecular Mechanisms of Purine and Pyrimidine Nucleotide Release;238
14.1;I. Introduction;238
14.2;II. Nucleotide Release Is a Feature of Living Cells;239
14.3;III. Mechanisms of Nucleotide Release;246
14.4;IV. Conclusion;264
14.5;Acknowledgments;265
14.6;References;266
15;Chapter 9: Impact of Ectoenzymes on P2 and P1 Receptor Signaling;280
15.1;I. Introduction;280
15.2;II. Enzymes Metabolizing Extracellular Nucleotides;281
15.3;III. Examples of Physiological Roles of Ectoenzymes in P2 and P1 Signaling;295
15.4;IV. Note on Ectonucleotidase Inhibitor Development;302
15.5;V. Conclusion;304
15.6;Acknowledgments;305
15.7;References;305
16;Chapter 10: Ectonucleotidases as Regulators of Purinergic Signaling in Thrombosis, Inflammation, and Immunity;318
16.1;I. Introduction;319
16.2;II. Purinergic Signaling: A Paradigm Linking Coagulation, Inflammation, and Immunity;320
16.3;III. Extracellular Nucleotides, Nucleosides, and Ectonucleotidases;320
16.4;IV. Purinergic Signaling Responses in the Vasculature and Immune Systems;323
16.5;V. Hemostasis and Thrombosis;325
16.6;VI. Inflammation;330
16.7;VII. Immunity;333
16.8;VIII. Disease Processes;336
16.9;IX. Conclusion;339
16.10;Acknowledgments;341
16.11;References;341
17;Chapter 11: P2X Receptors in Health and Disease;350
17.1;I. Introduction;351
17.2;II. Molecular Physiology of P2X Receptors;351
17.3;III. Distribution and Physiological Roles of P2X Receptors;356
17.4;IV. Pathophysiology of P2X Receptors;363
17.5;V. Conclusion;377
17.6;References;378
18;Chapter 12: Molecular Pharmacology, Physiology, and Structure of the P2Y Receptors;390
18.1;I. Introduction;391
18.2;II. Signaling Through Heterotrimeric G Proteins;391
18.3;III. The P2Y Receptors;392
18.4;IV. P2Y Receptor Structure;400
18.5;V. Selective P2Y Receptor Ligands as Pharmacological Tools;408
18.6;VI. Conclusions;415
18.7;Acknowledgments;415
18.8;References;416
19;Chapter 13: P2Y Receptors in Health and Disease;434
19.1;I. Introduction;435
19.2;II. P2Y Receptors in Platelet Activation;435
19.3;III. Clopidogrel for the Treatment of ACS and STEMI;436
19.4;IV. Aspirin and Clopidogrel Resistance;437
19.5;V. Novel ADP-Receptor Blockers for theTreatment of ACS;439
19.6;VI. Pulmonary Disease;442
19.7;VII. Dry Eye Disease;442
19.8;VIII. Hypertension;442
19.9;IX. Migraine and Vascular Pain;444
19.10;X. Atherosclerosis;444
19.11;XI. Osteoporosis;446
19.12;XII. Diabetes;446
19.13;XIII. Cardioprotection;448
19.14;XIV. Oncology;449
19.15;XV. Conclusion;449
19.16;References;450
20;Chapter 14: P2 Receptor Signaling in Neurons and Glial Cells of the Central Nervous System;458
20.1;I. Introduction;459
20.2;II. The Source and Fate of Extracellular ATP;459
20.3;III. Recombinant P2 Receptors;460
20.4;IV. Signaling via P2 Receptors;467
20.5;V. Pharmacology of the P2 Receptors;469
20.6;VI. Distribution of P2 Receptors in the CNS;471
20.7;VII. Role of P2 Receptors in Neuronal and Glial Functions in the CNS;473
20.8;VIII. Involvement of the P2 Receptors in Physiological and Pathophysiological CNS Functions—Possible Therapeutic Consequ;485
20.9;IX. Conclusion;490
20.10;Acknowledgments;490
20.11;References;492
21;Chapter 15: Role of Purinergic Receptors in CNS Function and Neuroprotection;512
21.1;I. Introduction;513
21.2;II. The Role of Purinergic Receptors in Neuronal Cell Function and Survival;514
21.3;III. The Role of Purinergic Receptors in Astrocyte Function and Survival;519
21.4;IV. The Role of Purinergic Receptors in Microglial Function;521
21.5;V. The Role of Purinergic Receptors in Oligodendrocyte Function and Survival;529
21.6;VI. Conclusion;530
21.7;References;532
22;Index;546
23;Recent Volumes in the Seria;558