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Research on purine derivatives as potent and selective modulators of physiologic functions has moved to center stage. This volume covers the biology and chemistry of purines and of their receptors broadly under these section headings: - Adenosine Receptors and Effector Systems - Adenine Nucleotide Receptors and Effector Systems - Phosphodiesterase Enzymes and Inhibitors The presentations focus on the potential development of clinically useful drugs and powerful agents that activate or block purinergic receptors or that inhibit phosphodiesterases. Xanthines (caffeine and theophylline) represent one class of such agents. This volume is for pharmacologists, biochemists, and medical chemists in research labs of universities, gov- ernment, and the pharmaceutical industry.


Research on purine derivatives as potent and selective modulators of physiologic functions has moved to center stage. This volume covers the biology and chemistry of purines and of their receptors broadly under these section headings: - Adenosine Receptors and Effector Systems - Adenine Nucleotide Receptors and Effector Systems - Phosphodiesterase Enzymes and Inhibitors The presentations focus on the potential development of clinically useful drugs and powerful agents that activate or block purinergic receptors or that inhibit phosphodiesterases. Xanthines (caffeine and theophylline) represent one class of such agents. This volume is for pharmacologists, biochemists, and medical chemists in research labs of universities, gov- ernment, and the pharmaceutical industry.
Content:
Front Matter....Pages i-xv
Front Matter....Pages 1-1
Adenosine Agonists and Antagonists....Pages 3-12
Intracellular and Extracellular Metabolism of Adenosine and Adenine Nucleotides....Pages 13-19
Adenosine Deaminase and Adenosine Transport Systems in the CNS....Pages 20-25
Transport Systems for Adenosine in Mammalian Cell Membranes....Pages 26-32
Formation of Adenosine in the Heart from Extracellular Adenine Nucleotides....Pages 33-40
Central Nervous System Effects of Adenosine....Pages 41-47
Adenosine Receptor Sub-types in Isolated Tissues: Antagonist Studies....Pages 48-53
Molecular Probes for Adenosine Receptors....Pages 54-64
Purification of A1 Adenosine Receptor of Rat Brain Membranes by Affinity Chromatography....Pages 65-68
Characteristics of A1 Adenosine Receptors and Guanine Nucleotide Binding Proteins Co-Purified from Bovine Brain....Pages 69-72
Antagonist Radioligand Binding to Solubilized Porcine Atrial A1 Adenosine Receptors....Pages 73-77
Isolation of an Adenosine Binding Protein Which Has Properties Expected of the A1 Adenosine Receptor....Pages 78-81
Identification of the A2 Adenosine Receptor Binding Subunit by Photoaffinity Crosslinking....Pages 82-85
Human Placental Adenosine A2-Like Binding Sites Properties and Homology with Mammalian and Avian Stress Proteins....Pages 86-89
Cardiac Interstitial Fluid Adenosine in Normoxia and Hypoxia....Pages 90-95
Rationale for the Use of Adenosine in the Diagnosis and Treatment of Cardiac Arrhythmias....Pages 95-99
The Central Adenosine System as a Therapeutic Target in Stroke....Pages 100-107
Adenosine-Mediated Vasoconstriction in the Skin Microcirculation....Pages 108-113
Adenosine is an Antiinflammatory Autocoid: Adenosine Receptor Occupancy Promotes Neutrophil Chemotaxis and Inhibits Superoxide Anion Generation....Pages 114-119
Beta Adrenergic Receptor Mediated Stimulation of Adenine Nucleotide Catabolism and Purine Release in Human Adipocytes....Pages 120-125
Front Matter....Pages 1-1
Structure Activity Relationships for Adenosine Antagonists....Pages 126-135
Structure Activity Relationships for Adenosine Agonists....Pages 136-145
The Design of a Series of Highly A2 Selective Adenosine Agonists....Pages 146-151
Adenosine Agonists. Characterization of the N6-Subregion of the Adenosine A2 Receptor via Molecular Modeling Techniques....Pages 152-157
Physiological and Biochemical Aspects of “P”-Site-Mediated Inhibition of Adenylyl Cyclase....Pages 158-165
Adenosine Receptors Mediating Inhibition of Peripheral and Central Neurons....Pages 166-173
Adenosine Receptors as Drug Targets: Fulfilling the Promise?....Pages 174-183
Mechanisms of Adenosine Action....Pages 184-193
Functional Roles of A1 and A2 Receptors in Rat Hippocampus and Striatum....Pages 194-199
Subclassification of Neuronal Adenosine Receptors....Pages 200-205
Effects of Adenosine on Mast Cells....Pages 206-212
The Role of Adenosine on the Gastric Acid Secretory Response....Pages 213-219
Adenosine Receptors and Signaling in the Kidney....Pages 220-225
Inhibition of the Function of Guanine Nucleotide Binding Proteins by the New Positive Inotropes....Pages 226-233
Blockade of Antigen Activated Signals by Xanthine Analogs in RBL-2H3 Cells: Evidence for a Novel Adenosine Receptor....Pages 233-238
Front Matter....Pages 239-239
Classification and Characterization of Purinoceptors....Pages 241-253
Structure Activity Relationships for Adenine Nucleotide Receptors on Mast Cells, Human Platelets, and Smooth Muscle....Pages 254-259
Modulation of Norepinephrine Release by ATP and Adenosine....Pages 260-265
The Phospholipase C Linked P2y-Purinergic Receptor....Pages 266-271
Roles of an ADP Receptor on the Platelet Surface in Mediating Aggregation and Fibrinogen Binding....Pages 272-278
Front Matter....Pages 279-279
Structural and Functional Characterization of Cyclic GMP-Stimulated Phosphodiesterases and Their Role in Intracellular Signal Transduction....Pages 281-289
Phosphodiesterase Genes from Flies to Mammals....Pages 290-296
Structure and Function of the High Affinity, Rolipram and RO 2-1724 Sensitive, cAMP Phosphodiesterases....Pages 297-302
Correlation of 3H-Rolipram Binding to a Cerebral cAMP Phosphodiesterase with Antidepressant Activity....Pages 303-308
Mechanism for Dual Regulation of the Particulate cGMP-Inhibited cAMP Phosphodiesterase in Rat Adipocytes by Isoproterenol and Insulin....Pages 309-314
Expression of Calmodulin-Dependent Cyclic Nucleotide Phosphodiesterase in Developing and Adult Rat Brain....Pages 315-322
Regulation of cAMP Metabolism in PC12 Cells by Type II (cGMP-Activatable) Cyclic Nucleotide Phosphodiesterase....Pages 323-328
cGMP-Binding Phosphodiesterase: Novel Effects of cGMP Binding on the Interaction Between Functional Domains in the Enzyme....Pages 329-335
Clinical Investigations with Phosphodiesterase Inhibitors....Pages 336-346
Chemical Probes of Type IV Phosphodiesterase: Design, Synthesis, and Characterization of (3H)-2Y186126 as a Radioligand for Sites Within Cardiac Membranes....Pages 347-352
Purification of a cGMP-inhibited cAMP Phosphodiesterase from Vascular Smooth Muscle....Pages 353-357
Low KmcAMP Phosphodiesterase Isozymes and Modulation of Tone in Vascular, Airway and Gastrointestinal Smooth Muscle....Pages 358-364
Structure Activity Relationships of Xanthines as Inhibitors of Cyclic Nucleotide Phosphodiesterases and as Antagonists of Adenosine Receptors....Pages 365-369
Mechanisms of Xanthine Actions in Models of Asthma....Pages 370-375
Back Matter....Pages 377-448


Research on purine derivatives as potent and selective modulators of physiologic functions has moved to center stage. This volume covers the biology and chemistry of purines and of their receptors broadly under these section headings: - Adenosine Receptors and Effector Systems - Adenine Nucleotide Receptors and Effector Systems - Phosphodiesterase Enzymes and Inhibitors The presentations focus on the potential development of clinically useful drugs and powerful agents that activate or block purinergic receptors or that inhibit phosphodiesterases. Xanthines (caffeine and theophylline) represent one class of such agents. This volume is for pharmacologists, biochemists, and medical chemists in research labs of universities, gov- ernment, and the pharmaceutical industry.
Content:
Front Matter....Pages i-xv
Front Matter....Pages 1-1
Adenosine Agonists and Antagonists....Pages 3-12
Intracellular and Extracellular Metabolism of Adenosine and Adenine Nucleotides....Pages 13-19
Adenosine Deaminase and Adenosine Transport Systems in the CNS....Pages 20-25
Transport Systems for Adenosine in Mammalian Cell Membranes....Pages 26-32
Formation of Adenosine in the Heart from Extracellular Adenine Nucleotides....Pages 33-40
Central Nervous System Effects of Adenosine....Pages 41-47
Adenosine Receptor Sub-types in Isolated Tissues: Antagonist Studies....Pages 48-53
Molecular Probes for Adenosine Receptors....Pages 54-64
Purification of A1 Adenosine Receptor of Rat Brain Membranes by Affinity Chromatography....Pages 65-68
Characteristics of A1 Adenosine Receptors and Guanine Nucleotide Binding Proteins Co-Purified from Bovine Brain....Pages 69-72
Antagonist Radioligand Binding to Solubilized Porcine Atrial A1 Adenosine Receptors....Pages 73-77
Isolation of an Adenosine Binding Protein Which Has Properties Expected of the A1 Adenosine Receptor....Pages 78-81
Identification of the A2 Adenosine Receptor Binding Subunit by Photoaffinity Crosslinking....Pages 82-85
Human Placental Adenosine A2-Like Binding Sites Properties and Homology with Mammalian and Avian Stress Proteins....Pages 86-89
Cardiac Interstitial Fluid Adenosine in Normoxia and Hypoxia....Pages 90-95
Rationale for the Use of Adenosine in the Diagnosis and Treatment of Cardiac Arrhythmias....Pages 95-99
The Central Adenosine System as a Therapeutic Target in Stroke....Pages 100-107
Adenosine-Mediated Vasoconstriction in the Skin Microcirculation....Pages 108-113
Adenosine is an Antiinflammatory Autocoid: Adenosine Receptor Occupancy Promotes Neutrophil Chemotaxis and Inhibits Superoxide Anion Generation....Pages 114-119
Beta Adrenergic Receptor Mediated Stimulation of Adenine Nucleotide Catabolism and Purine Release in Human Adipocytes....Pages 120-125
Front Matter....Pages 1-1
Structure Activity Relationships for Adenosine Antagonists....Pages 126-135
Structure Activity Relationships for Adenosine Agonists....Pages 136-145
The Design of a Series of Highly A2 Selective Adenosine Agonists....Pages 146-151
Adenosine Agonists. Characterization of the N6-Subregion of the Adenosine A2 Receptor via Molecular Modeling Techniques....Pages 152-157
Physiological and Biochemical Aspects of “P”-Site-Mediated Inhibition of Adenylyl Cyclase....Pages 158-165
Adenosine Receptors Mediating Inhibition of Peripheral and Central Neurons....Pages 166-173
Adenosine Receptors as Drug Targets: Fulfilling the Promise?....Pages 174-183
Mechanisms of Adenosine Action....Pages 184-193
Functional Roles of A1 and A2 Receptors in Rat Hippocampus and Striatum....Pages 194-199
Subclassification of Neuronal Adenosine Receptors....Pages 200-205
Effects of Adenosine on Mast Cells....Pages 206-212
The Role of Adenosine on the Gastric Acid Secretory Response....Pages 213-219
Adenosine Receptors and Signaling in the Kidney....Pages 220-225
Inhibition of the Function of Guanine Nucleotide Binding Proteins by the New Positive Inotropes....Pages 226-233
Blockade of Antigen Activated Signals by Xanthine Analogs in RBL-2H3 Cells: Evidence for a Novel Adenosine Receptor....Pages 233-238
Front Matter....Pages 239-239
Classification and Characterization of Purinoceptors....Pages 241-253
Structure Activity Relationships for Adenine Nucleotide Receptors on Mast Cells, Human Platelets, and Smooth Muscle....Pages 254-259
Modulation of Norepinephrine Release by ATP and Adenosine....Pages 260-265
The Phospholipase C Linked P2y-Purinergic Receptor....Pages 266-271
Roles of an ADP Receptor on the Platelet Surface in Mediating Aggregation and Fibrinogen Binding....Pages 272-278
Front Matter....Pages 279-279
Structural and Functional Characterization of Cyclic GMP-Stimulated Phosphodiesterases and Their Role in Intracellular Signal Transduction....Pages 281-289
Phosphodiesterase Genes from Flies to Mammals....Pages 290-296
Structure and Function of the High Affinity, Rolipram and RO 2-1724 Sensitive, cAMP Phosphodiesterases....Pages 297-302
Correlation of 3H-Rolipram Binding to a Cerebral cAMP Phosphodiesterase with Antidepressant Activity....Pages 303-308
Mechanism for Dual Regulation of the Particulate cGMP-Inhibited cAMP Phosphodiesterase in Rat Adipocytes by Isoproterenol and Insulin....Pages 309-314
Expression of Calmodulin-Dependent Cyclic Nucleotide Phosphodiesterase in Developing and Adult Rat Brain....Pages 315-322
Regulation of cAMP Metabolism in PC12 Cells by Type II (cGMP-Activatable) Cyclic Nucleotide Phosphodiesterase....Pages 323-328
cGMP-Binding Phosphodiesterase: Novel Effects of cGMP Binding on the Interaction Between Functional Domains in the Enzyme....Pages 329-335
Clinical Investigations with Phosphodiesterase Inhibitors....Pages 336-346
Chemical Probes of Type IV Phosphodiesterase: Design, Synthesis, and Characterization of (3H)-2Y186126 as a Radioligand for Sites Within Cardiac Membranes....Pages 347-352
Purification of a cGMP-inhibited cAMP Phosphodiesterase from Vascular Smooth Muscle....Pages 353-357
Low KmcAMP Phosphodiesterase Isozymes and Modulation of Tone in Vascular, Airway and Gastrointestinal Smooth Muscle....Pages 358-364
Structure Activity Relationships of Xanthines as Inhibitors of Cyclic Nucleotide Phosphodiesterases and as Antagonists of Adenosine Receptors....Pages 365-369
Mechanisms of Xanthine Actions in Models of Asthma....Pages 370-375
Back Matter....Pages 377-448
....
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