Extracellular Nucleotides and Nucleosides: Release, Receptors, and Physiological & Pathophysiological Effects: Release, Receptors, and Physiological & Pathophysiological Effects
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Table of contents
- Copyright Pageiv
- Contentsvii
- Dedicationv
- Contributorsxiii
- Forewordxvii
- Prefacexxiii
- Previous Volumes in Seriesxxv
- Chapter 1. Introduction: ATP and its Metabolites as Potent Extracellular Agents1
- I. Early Studies2
- II. Purinoceptor Subtypes3
- III. Distribution and Roles of Purinoceptor Subtypes8
- IV. Pathophysiological Roles of Purinoceptors and Therapeutic Potential15
- References19
- Part I: Molecular Biology, Cell Biology, and Biochemistry29
- Chapter 2. Cellular Mechanisms and Physiology of Nucleotide and Nucleoside Release from Cells: Curre31
- I. Introduction32
- II. Possible Cellular Mechanisms of ATP Release from Cells35
- III. Indirect Pharmacological Screening for Extracellular Nucleotide and Nucleoside Release and Sign42
- IV. Novel Assays to Detect ATP Release from Cells43
- V. Future Directions53
- References55
- Chapter 3. Molecular and Biological Properties of P2Y Receptors59
- I. Introduction59
- II. Overview of the Pharmacological Properties of P2Y Receptors60
- III. The P2Y Receptor Family68
- IV. Concluding Comments85
- References86
- Chapter 4. Extracellular ATP-gated P2X Purinergic Receptor Channels97
- I. Summary98
- II. Extracellular ATP-Activated Ion Channels99
- III. Molecular Cloning100
- IV. Determination of Patterns and Levels of Expression in Specific Cells and Tissues112
- V. Biophysical Properties of P2XRS in Native and Heterologous Cells118
- VI. Homo- and Heteromultimerization of P2XRS122
- VII. Biochemistry of P2XRS Channels in Native and Heterologous Cells125
- VIII. Epithelial P2XRS129
- IX. Physiological Roles for P2XRS in Endothelia, Vascular Smooth Muscle, and Specialized Neurons135
- X. Future Directions141
- References142
- Chapter 5. Molecular and Cell Biology of Adenosine Receptors151
- I. Introduction152
- II. Molecular Pharmacology153
- III. Adenosine Receptor-Effector Coupling and Intracellular Signaling159
- IV. Adenosine Receptors in Health and Disease163
- V. Concluding Remarks172
- References172
- Chapter 6. Relating the Structure of ATP-gated Ion Channel Receptors to their Function183
- I. Introduction183
- II. Subunit Topology185
- III. Composition and Stoichiometry of Receptor-Channel Complexes187
- IV. Transmembrane Domains187
- V. Extracellular Domains194
- VI. Intracellular Domains197
- VII. Future Directions198
- References199
- Part II: Physiology and Pathophysiology203
- Chapter 7. Epithelial Purinergic Receptors and Signaling in Health and Disease205
- I. Introduction205
- II. The Epithelium as an Ideal Autocrine and Paracrine Signaling Microenvironment206
- III. Integrated Purinergic Signaling in Model Epithelium211
- IV. Paradigms for Purinergic Signaling in Diseased Epithelium231
- V. Future Directions235
- References237
- Chapter 8. Nucleotide Release and Purinergic Signaling in the Vasculature Driven by the Red Blood C243
- I. Introduction243
- II. The Source of Soluble Mediators that Regulate EDRF Synthesis244
- III. Evidence for the Release of ATP from Red Blood Cells in Response to Physiological Stimuli245
- IV. Role of Red Blood Cells-Derived ATP in Specific Vascular Beds247
- V. Proposed Signal-Transduction Pathway for ATP Release from Red Blood Cells258
- VI. Conclusions262
- References263
- Chapter 9. A Purine Signal for Functional Hyperemia in Skeletal and Cardiac Muscle269
- I. Introduction270
- II. Functional Hyperemia in Skeletal Muscle275
- III. Functional Hyperemia in Cardiac Muscle281
- IV. ATP Release Associated with Membrane Depolarization288
- V. Purine Signal from Erythrocytes292
- VI. Physical Forces Contributing to the Purine Signal294
- VII. Discussion295
- VIII. Summary and Conclusions298
- References299
- Chapter 10. Purinergic Receptors in the Nervous System307
- I. Introduction308
- II. Peripheral Neurotransmission310
- III. Sensory and Autonomic Ganglia314
- IV. Central Nervous System322
- V. Future Developments340
- References340
- Chapter 11. Purinergic (P2) Receptors in the Kidney369
- I. Introduction369
- II. The Kidney372
- III. The Glomerulus373
- IV. The Proximal Tubule377
- V. The Loop of Henle380
- VI. The Distal Tubule and Collecting Duct382
- VII. Functional Implication of Renal Epithelial P2 Receptors384
- References386
- Chapter 12. Purinergic Receptors and Hepatobiliary Function395
- I. Introduction395
- II. Hepatic Purinergic Receptor Expression396
- III. ATP Release Mechanisms397
- IV. Regulation of Nucleotide Release399
- V. Degradation and Reuptake Pathways404
- VI. Potential Physiological Roles for Hepatic Purinergic Signaling407
- VII. Hepatic Glucose Metabolism407
- VIII. Autocrine Regulation of Cell Volume408
- IX. Paracrine Coordination of Calcium Signaling409
- X. Hepatobiliary Coupling and Bile Formation409
- XI. Conclusion411
- References411
- Chapter 13. ATP in the Treatment of Advanced Cancer415
- I. Introduction415
- II. Pronounced Depletion of Purines in Aging and Advanced Disease416
- III. Ability of Exogenously Administered ATP to Expand Organ, Blood, and Plasma (Extracellular) Pool435
- IV. Summary of Previous ATP Cancer Trials438
- V. Conclusions: Administration of ATP in the Treatment of Advanced Cancer442
- VI. The Future443
- References443
- Chapter 14. Purinergic Receptors in the Glomerulus and Vasculature of the Kidney453
- I. Introduction453
- II. P2 Receptor Distribution Along the Renal Vasculature and Glomerulus454
- III. Renal Vascular Response to P2 Receptor Activation454
- IV. Renal Vascular Signaling Mechanisms462
- V. Renal Vascular Response to P2 Receptor Activation465
- VI. Regulation of Renin Secretion by Adenosine467
- VII. General Hypothesis on the Role of P1 and P2 Receptors in the Physiological Regulation of Renal467
- VIII. Measurement of Purine Nucleotides and Nucleosides in Renal Interstitial Fluid471
- IX. Final Comments472
- References472
- Index479
- Color Plate Section499
Purinergic receptors are proteins that bind ATP as their extracellular ligand. Once thought only as an intracellular molecule that provides energy, ATP is also now considered an essential autocrine/paracrine agonist that acts extracellularly within tissues and tissue microenvironments. Receptors for ATP and its metabolites, so-called "purinergic receptors," are essential membrane receptors that transduce the extracellular signal carried by ATP. Many cell types or tissues express multiple types of these receptors, often on the same cell. This volume will cover the history and overall impact of extracellular ATP signaling, methods to detect ATP release and signaling, the molecular and cell biology of purinergic receptors, the pharmacology of purinergic receptors, the ion channel biophysics and biochemistry of P2X purinergic receptor channels, and the physiology and pathophysiology of purinergic receptors.
Key Features
* Organized and written by world-renowned experts
* Covers state-of-the-art experimental methods
* Has broad appeal to basic and clinical scientists, the biotch industry and pharmaceutical research companies
Key Features
* Organized and written by world-renowned experts
* Covers state-of-the-art experimental methods
* Has broad appeal to basic and clinical scientists, the biotch industry and pharmaceutical research companies