Platelets and Their Factors
(Sprache: Englisch)
Platelets playa fundamental, life-saving role in hemostasis and blood clotting at sites of vascular injury. Unwanted platelet activation and arterial thombus formation are, however, implicated in the onset of myocardial infarction, stroke, and other...
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Platelets playa fundamental, life-saving role in hemostasis and blood clotting at sites of vascular injury. Unwanted platelet activation and arterial thombus formation are, however, implicated in the onset of myocardial infarction, stroke, and other cardiovascular diseases. Acceptance that platelets play a major role in the pathogenesis of atherosclerosis including coronary heart disease has revolutionized the pharmacological treatment of cardiovascular diseases, and aspirin is now an essential antiplatelet drug and the golden standard for future developments. Yet the search for better and perhaps safer antiplatelet drugs is one of the most active areas of investigation in both basic and clinical research. Platelets, especially human platelets, have also emerged as one of the major models for the study of inter- and intracellular signal transduction pathways. Many biochemists, cell biologists, pharmacologists, pathologists, hematologists, and cardiologists find platelets useful for studying processes such as adhesion, inside-out and outside-in signalling through the plasma membrane, channels, calcium homeostasis, protein kinases, the network of intracellular signal transduction cascades, and the release of vasoactive substances. The aim of the editors has been to compile chapters summarizing the current state-of-the-art information on the biochemistry, cell biology, pharmacology, and physiologic and pathophysiologic roles of human platelets. We hope that this volume represents the major aspects of current platelet research although it is perhaps inevitable that certain areas are covered less thoroughly than others. We would like to acknowledge the excellent help and support of the Springer-Verlag staff, in particular that of Ms. Doris Walker.
Inhaltsverzeichnis zu „Platelets and Their Factors “
Section I: Platelet Development, Morphology and Physiology1 Megakaryocytopoiesis: The Megakaryocyte/Platelet Haemostatic Axis
A. Introduction
B. Megakaryocyte Anatomy
I. Structure
II. Site of Platelet Production
III. Ploidy
C. Megakaryocytopoiesis and Thrombopoiesis
I. Perturbations of the Steady State
II. Megakaryocyte Progenitor Cells
III. Megakaryocyte Growth Factors
IV. Thrombopoietin/cMpl Ligand
V. Negative Regulation of Megakaryocytopoiesis
D. Signal Transduction Events and Mechanisms of Polyploidisation
I. Involvement of Protein Kinase C in Megakaryocyte Differentiation
II. Induction of Tyrosine Phosphorylation by TPO
III. Cell Cycle Control and Polyploidisation
E. Megakaryocytes in Atherosclerosis
F. Conclusion
- References
2 Human Platelet Morphology/Ultrastructure
A. General Morphology: Shape and Properties of Platelets
B. Electron-Microscopic Techniques
C. Morphometric Data
D. Ultrastructure of Platelets
I. Cytosol and Cytoskeleton
1. Cytosol
2. Submembranous Cytoskeleton
3. Contractile Gel
II. Plasmalemma and Surface
III. Surface-Connected Membranes
1. Surface-Connected (Open Canalicular) System
2. Coated Membranes
IV. Cell Organelles
1. Mitochondria
2. Dense Tubular System
3. Alpha-Granules
4. Dense Granules
5. Lysosomes and Peroxisomes
E. Functional Morphology
I. Focal Adhesion Contacts
II. Internalization and Endocytosis
1. Receptor Transport and Membrane Recycling
2. Internalization of Ligands by the Contractile Gel
III. Exocytosis
1. Secretory Pathway
2. Shedding of "Microparticles"
F. Synopsis and Conclusions
- References
3 Platelet Adhesion
A. Introduction
B. The Vessel Wall
C. Platelet Adhesion Under Flow Conditions
D. Platelet Adhesion to the Adhesive Proteins
I. Von Willebrand Factor
II. Collagen
III. Fibronectin
IV. Fibrin(ogen)
V. Other Proteins
1. Laminin
2. Thrombospondin
3. Proteoglycans
E. Conclusion
- References
4 Platelet Aggregation
A. Introduction
B. Mechanism of
... mehr
Platelet Aggregation
I. The Glycoprotein IIb-IIIa Complex
II. Adhesive Ligands of the GPIIb-IIIa Complex
III. Redistribution of the GpIIb-IIIa Complex and Internalization of the Ligands
C. Platelet Aggregation Testing
I. Sample Preparation
II. Optical Aggregometry
III. Lumi-aggregometry
IV. Determination of Platelet Aggregation by Particle Counting 90
V. Potential and Limitations of Platelet Aggregation Testing
D. Inhibition of Platelet Aggregation as a Therapeutic Principle
E. Conclusions
- References
Section II: Platelet Biochemistry, Signal Transduction
5 Platelet Receptors: The Thrombin Receptor
A. Introduction
B. The Seven-Transmembrane Domain Receptor
I. Structure and Activation Mechanism
II. Receptor Desensitization and Resensitization
C. Glycoprotein Ib
D. Receptor Signaling and Platelet Responses
E. Thrombin Receptor Inhibitors
- References
6 Platelet ADP/Purinergic Receptors
A. Introduction
B. Platelet Responses to ADP
I. Platelet Functions
1. Shape Change
2. Binding of Fibrinogen
3. ADP-Induced Platelet Aggregation
4. Desensitization
II. Signal Transduction
1. Changes in Cytosolic Free Calcium Concentration
2. Changes in Inositol Phospholipids
3. Inhibition of Adenylyl Cyclase
4. Involvement of G Proteins
C. Platelet ADP Receptors
I. Binding Studies
II. ADP-Binding Proteins
III. The P2 Purinoceptor Family
IV. Current Hypothesis of a Two-Receptor Model
V. Future Perspectives
D. Conclusions
- References
7 Platelet Prostaglandin Receptors
A. Introduction
B. Thromboxane A2 Receptor
I. Structure and Ligand Binding Specificity
II. Signal Transduction
III. Regulation
C. Prostacyclin Receptor
I. Structure and Ligand Binding Specificity
II. Signal Transduction
III. Regulation
D. Prostaglandin D Receptor
I. Structure
II. Ligand Binding Specificity and Signal Transduction
E. Prostaglandin E Receptor Subtype; the EP3 Receptor
- References
8 Platelet Adhesion and Aggregation Receptors
A. Introduction
B. Platelet Surface Glycoproteins
C. The Glycoprotein Ib-V-IX Complex
I. Introduction
1. Glycoprotein Ib?
2. Glycoprotein Ib?
3. Glycoprotein IX
4. Glycoprotein V
5. Polymorphism Within GPIb?
II. Function of the Glycoprotein Ib-V-IX Complex
1. Bleeding Disorders
a) Bernard-Soulier Syndrome
b) Platelet-Type von Willebrand's Disease
2. GPIb-vWf Binding
3. Non-physiological Activators of the GPIb/vWF Axis
III. Expression of GPIb-V-IX
D. GPIIb-IIIa
E. GPIa-IIa
F. GPIc-IIa
G. GPIc'-IIa
H. CD36 (GPIIIb or GPIV)
I. P-selectin (CD62, GMP-140, PADGEM)
J. PECAM-1 (CD31)
K. Inhibition of Platelet Adhesion/Aggregation as a Prophylactic Tool or for Treatment of Acute Thrombotic Events
- References
9 Platelet G Proteins and Adenylyl and Guanylyl Cyclases
A. Introduction
B. G Proteins
I. General Considerations
1. Activation of G Proteins
2. Diversity of G Proteins
3. Structure of G Proteins
4. Co- and Posttranslational Modifications of Platelet G Proteins
II. G Proteins Expressed in Platelets
III. G Proteins as Modulators of Platelet Activation
1. Platelet-Activating G Proteins
2. Platelet-Inhibiting G Proteins
C. Adenylyl Cyclases
D. Guanylyl Cyclases
I. Membrane-Bound Guanylyl Cyclases
II. Soluble Guanylyl Cyclases
1. Regulation of Soluble Guanylyl Cyclases
2. Biosynthesis of Nitric Oxide
III. cGMP Receptor Proteins
1. cGMP-Dependent Protein Kinases
2. cGMP-Gated Channels
E. Physiological Role of Cyclic Nucleotides in Platelets
I. cGMP-Formation in Platelets
II. cGMP- and cAMP-Dependent Protein Kinases in Platelets
III. Substrates for cAMP- and cGMP-Dependent Protein Kinases in Platelets
IV. Cellular Responses Leading to Platelet Inhibition
- References
10 Platelet Phosphodiesterases
A. Introduction
B. Catalytic and Regulatory Properties of Human Platelet Phosphodiesterases
I. cGMP-Stimulated Phosphodiesterase
II. cGMP-Inhibited Phosphodiesterase
III. cGMP-Specific Phosphodiesterase
C. Synergistic Inhibition of Platelet Function by Cyclic Nucleotide Elevating Agents
D. Regulation of Platelet Phosphodiesterases by Insulin
E. Effect of Phosphodiesterase Inhibitors on Platelet Function
I. General Aspects
II. Specificity
F. Concluding Remarks
- References
11 Platelet Phospholipases C and D
A. Introduction
B. Receptor-Mediated Activation of Phosphoinositide-Specific Phospholipase C
I. Activation of Phosphoinositide-Specific Phospholipase C in Platelets
II. Formation of Second Messengers
1. Inositol 1,4,5-trisphosphate
2. 1,2-Diacylglycerol
3. Phosphatidic Acid and Lysophosphatidic Acid
III. Modulation of Phosphoinositide-Specific Phospholipase C
C. Regulation of Phosphoinositide-Specific Phospholipase C
I. Multiplicity of Phosphoinositide-Specific Phospholipase C
II. G-Protein-Mediated Phospholipase C-? Activation
III. Tyrosine Kinase-Mediated Phospholipase C-?Activation
D. Roles and Regulation of Phospholipase D in Platelet Activation
I. Activation of Phospholipase D in Platelets
II. Regulation of Phospholipase D Activity
E. Remarks
- References
12 Protein Kinase C and Its Interactions with Other Serine-Threonine Kinases
A. Introduction and Definition
B. Molecular Structure and Heterogeneity
C. PKC Activation by Lipid Mediators in Platelets
D. PKC Substrates, Binding Proteins, and Translocation
E. Functional Roles for PKC in Platelets
F. Relation of PKC Activation to Other Platelet Serine-Threonine Kinases and Their Effectors
G. Abnormalities of Platelet PKC in Disease
H. Summary and Future Areas of Research
- References
13 Platelet Protein Tyrosine Kinases
A. Background
B. Protein Tyrosine Kinases in Platelets
I. Src Family Kinases
1. Src
2. Other Src Family Members
II. Syk
III. JAK Family Kinases
IV. Focal Adhesion Kinase (FAK)
V. Receptor Protein Tyrosine Kinases
C. Potential Roles of Protein Tyrosine Kinases in Platelet Functions
I. Second Messenger Pathways
1. Phospholipases
2. Phosphoinositide 3-Kinase
3. GTP-Binding Proteins
4. Calcium
5. Cyclic Nucleotides
II. Platelet Responses
1. Shape Change
2. Aggregation
3. Adhesion
- References
14 Protein Phosphatases in Platelet Function
A. Introduction
B. Protein Serine/Threonine Phosphatases in Platelets
I. Classification of Serine/Threonine Protein Phosphatases
II. Inhibitors of Protein Serine/Threonine Phosphatases
III. The Presence of Protein Serine/Threonine Phosphatases in Platelets
IV. Effect of Okadaic Acid and Calyculin A in Platelets
V. Dephosphorylation of Cofilin in Platelets
VI. Protein Serine/Threonine Phosphatases in Platelets: Concluding Remarks
C. Protein Tyrosine Phosphatases
I. Classification of Protein Tyrosine Phosphatases
II. Distribution of Protein Tyrosine Phosphatases in Platelets
III. Regulation of Tyrosine Phosphorylation by Irreversible Platelet Aggregation
IV. Effect of Vanadate and Its Derivatives in Platelets
V. Effect of Phenylarsine Oxide in Platelets
VI. Possible Role of Protein Tyrosine Phosphatases in Ca2+ Entry
VII. Regulation of Protein Tyrosine Phosphatases by Serine/Threonine Phosphorylation
VIII. Protein Tyrosine Phosphatases in Platelets: Concluding Remarks
D. Dual Specificity Protein Phosphatases
E. Concluding Remarks
- References
15 Ca2+ Homeostasis in Human Platelets
A. Introduction
I. Ca2+ Homeostasis
B. Maintenance of Low Cytosolic Ca2+ Concentrations
I. Platelet SERCAs
II. Membrane Organisation, Properties and Regulation of Platelet SERCAs
III. Organellar Distribution of Platelet SERCA Pumps
IV. Plasma Membrane Calcium ATPases
V. Platelet PMCAs
VI. Na+/Ca2+ Exchanger
C. Mechanisms of Ca2+ Elevation in Platelets
I. Ca2+ Release from Intracellular Stores
1. Inositol (1,4,5) Trisphosphate
2. General Properties of IP3Rs
3. Platelet IP3Rs
4. In(1,4,5)P3-Induced Ca2+ Release from Platelet Intracellular Stores
II. Nature of Ca2+ Release from Intracellular Stores
III. Ca2+ Oscillations in Platelets
IV. Ca2+ Influx Mechanisms
V. Capacitative or Store-Regulated Ca2+ Entry
VI. Possible Direct Involvement of Second Messengers in Ca2+ Entry
VII. Integrin-Associated Plasma Membrane Ca2+ Flux
VIII. Ca2+ Influx Via Receptor-Operated Ca2+ Channel (ROC)
IX. Cyclic Nucleotide Effects on Ca2+ Influx
- References
16 Regulation of Platelet Function by Nitric Oxide and Other Nitrogen- and Oxygen-Derived Reactive Species
A. Introduction
B. A Historical Perspective
C. Nitric Oxide Synthase Isoenzymes
I. General Characteristics
II. Platelet Nitric Oxide Synthase
III. The Endothelial NOS
IV. Nitric Oxide Synthase Reaction
V. Metabolic Fate of NO
VI. Interactions of NO with Biomolecules
VII. Nitric Oxide - Physiological Regulator of Platelet Function
VIII. Role of NO in the Pathogenesis of Vascular Disorders
IX. Pharmacological Regulation of Platelet Function by NO Gas and NO Donor Drugs
D. Other Oxygen- and Nitrogen-Derived Reactive Species
I. Mechanisms of Action of Oxygen-Derived Radicals on Platelets
1. Thromboxane Generation
2. Cyclic Nucleotides
3. Stimulation of Platelet Serotonin Transport
4. Activation of Platelet Receptors
5. Formation of Nitric Oxide Donors
E. Conclusions
- References
17 Platelet 5-Hydroxytryptamine Transporters
A. Introduction
B. The Plasma Membrane 5-Hydroxytryptamine Transporter (SERT)
I. Ionic Requirements
1. Coupling to Na+
2. Coupling to Cl-
3. Coupling to K+
II. Reversal of Transport
III. Mechanism
IV. Purification
V. Cloning
VI. Regulation
C. Dense Granule Membrane Vesicles
I. Driving Forces
II. Purification
III. Cloning
- References
Section III: Platelet-Derived Factors
18 Dense Granule Factors
A. Introduction
B. Contents of Platelets
I. Nucleotides
II. Divalent Cations
III. Amines
IV. Other
C. Storage Mechanisms
D. Species Differences
E. Membrane Proteins
F. Discussion and Comments
- References
19 Protein Granule Factors
A. Introduction
B. Platelet Proteins
C. Platelet-Derived Growth Factors
D. Thrombospondin
E. Proteins Similar or Identical to Plasma Proteins
F. Enzymes
G. Summary and Conclusions
- References
20 Lysosomal Storage
A. Introduction
I. Lysosomes in General
II. Platelet Lysosomes
B. Lysosomal Hydrolases in Platelets
I. Glycosidases
1. Secretion
2. Subcellular Localization
II. Proteinases
III. Phospholipases
IV. Other
C. Lysosomal Membrane Proteins
D. Discussion and Comments
- References
21 Thromboxane A2 and Other Eicosanoids
A. Introduction
B. Platelet Arachidonic Acid Metabolism
I. Metabolites
II. Sources of Arachidonic Acid
III. Release of Arachidonic Acid
1. Phospholipase A2
2. Other Routes of Arachidonic Acid Liberation
C. Eicosanoids Affecting Platelet Function
I. Thromboxane A2
1. Introduction
a) Thromboxane A2 Receptors
b) Signal Transduction
- Intracellular Calcium
- Alkalinization of Intraplatelet pH
- Protein Kinase C Activation
- Tyrosine Phosphorylation
- Myosin Light Chain Kinase
II. Prostacyclin (PGI2, Epoprostanol)
III. 8-Epi-prostaglandin F2?
IV. Prostaglandin D2 (PGD2)
V. 12-Hete (12-Hydroxyeicosatetraenoic Acid)
D. Alterations in Thromboxane A2 Synthesis in Disease States
I. Diabetes Mellitus
II. Acute Coronary Artery Syndromes
III. Pregnancy-Induced Hypertension
IV. Cerebral Ischemia
V. Homocystinuria
VI. Sickle Cell Disease
VII. Effects of Fish Oils
E. Alterations in Thromboxane A2 Receptors in Disease States
I. Acute Coronary Artery Syndromes
II. Pregnancy-Induced Hypertension
III. Diabetes Mellitus
IV. Regulation by Androgenic Steroids
F. Aspirin, Thromboxane Synthase Inhibitors, and Thromboxane A2 Receptor Antagonists in Coronary Artery Disease
- References
22 Platelet-Activating Factor: Biosynthesis, Biodegradation, Actions
A. Introduction
B. Biosynthesis of PAF in Mammalian Cells
C. Catabolism of PAF in Mammalian Cells
D. PAF and Bacteria
E. PAF and Yeast Cells, Protozoans, Amoebas, and Parasites
F. Effects of PAF on Cell Proliferation
G. Some Effects of PAF on Several Cell Functions and Tissue Structures
H. Conclusion
- References
23 Qualitative and Quantitative Assessment of Platelet Activating Factors
A. PAF Molecular Diversity
B. Estimation of PAF Activity by Bioassay
I. Platelet Bioassay
1. Rabbit Platelet Bioassay
2. Platelet Desensitization
3. PAF Carriers in Platelet Bioassay
4. PAF Molecular Diversity in Platelet Bioassay
II. Other
C. Estimation of PAF Activity by Radioimmunoassay (RIA)
I. RIA Development and Use
II. PAF Molecular Diversity in RIA
D. Estimation of PAF by Radioreceptor Assay
E. Estimation of PAF Based on [3H]Acetate Incorporation
F. Analysis of PAF by Mass Spectrometry
I. Analysis of Intact PAF
II. Analysis of PAF After Derivatization
G. Concluding Comments
- References
24 Biosynthetic Inhibitors and Receptor Antagonists to Platelet Activating Factor
A. PAF: Historical Perspective and Pathology
B. Biosynthesis Inhibitors
I. Phospholipase PLA2 Inhibitors
II. Lyso-PAF-Transferase Inhibitors
C. Preclinical and Clinical PAF Receptor Antagonists
I. Abbott Laboratories
II. Alter S.A
III. Boehringer Ingelheim KG
IV. British Biotechnology Ltd
V. Eisai Co., Ltd
VI. Fujisawa Pharmaceutical Co
VII. Hoffmann-La Roche and Co., Ltd
VIII. Leo Pharmaceutical Products Ltd
IX. Merck Sharp and Dohme Research Laboratories
X. Ono Pharmaceutical Co., Ltd
XI. Pfizer Laboratories
XII. Rhône-Poulenc Santé Laboratories
XIII. Sandoz Research Institute
XIV. Sanofi Research
XV. Schering-Plough Research Institute
XVI. Solvay Pharma Laboratories
XVII. Sumitomo Pharmaceuticals Co., Ltd
XVIII. Takeda Chemical Co., Ltd
XIX. Uriach S.A
XX. Yamanouchi Pharmaceutical Company
XXI. Yoshitomi Pharmaceutical Industries Ltd
D. Conclusions
- References
Section IV: Clinical Aspects of Platelets and Their Factors
25 Platelets and the Vascular System: Atherosclerosis, Thrombosis, Myocardial Infarction
A. Introduction
B. Atherosclerosis
C. Thrombosis
D. Myocardial Infarction
E. Methodology of Radiolabeling of Platelets
F. Studies with Radiolabeled Platelets
I. Platelet Kinetics
II. Imaging
1. Atherosclerosis
2. Thrombosis
3. Myocardial Infarction
G. Platelet Aggregation
H. Conclusions
- References
26 Platelets, Vessel Wall, and the Coagulation System
A. Platelet-Endothelium Interaction
I. Role of Platelets in Maintaining Vascular Integrity
II. Control of Platelet Reactivity by Endothelial Cells
1. 13-Hydroxy-octadecadienoic Acid (13-HODE) - An Antiadhesive Fatty Acid Metabolite
2. Endothelium-Derived Platelet Inhibitors
3. Platelet Effects on PGI2 and EDRF/NO Synthesis
4. Mechanisms of Platelet Inhibition by PGI2 and EDRF/NO
5. Endothelial-Bound Antiplatelet Factors
6. Platelet Adhesion to Endothelial Cells
III. Platelet-Mediated Inflammatory and Procoagulant Alterations of Endothelial Cells
B. Platelets and Coagulation
I. Membrane-Dependent Reactions in Blood Coagulation
II. Platelet Procoagulant Activity
III. Mechanisms Involved in the Maintenance of Membrane Lipid Asymmetry
IV. Mechanisms Involved in the Expression of Procoagulant Activity
V. Platelet Microvesicles
VI. Platelets and Coagulation Disorders
1. Scott Syndrome
2. Antiphospholipid Syndrome
3. Factor V Quebec
VII. Anticoagulant Activities of Platelets and Microvesicles
VIII. Role of Platelets in Fibrinolysis
- References
27 Platelet Flow Cytometry - Adhesive Proteins
A. Introduction
I. Procedures for the Diagnosis of Platelet Disease States
1. Problems
2. Requirements
B. Single Platelet Flow Cytometry (SPFC)
I. Principle
II. Pitfalls and Standardization Requirements
III. Assay Systems
C. Platelet Adhesion Molecules as Diagnostic Targets
I. Megakaryocytic Conditioning
II. Platelet Membrane Processing
III. Defining Diagnostic Epitopes
1. The Constitutive Stain
2. The Functional Stain
IV. Platelet-Leukocyte Coaggregates
D. Applications in Platelet Pathology
I. Hemorrhagic Diathesis
II. Thrombotic Diathesis
III. Inflammation
E. Pharmacology
- References
28 Pathological Aspects of Platelet-Activating Factor (PAF)
A. Introduction
B. Involvement of PAF in Inflammatory and Allergic Responses
I. Inflammatory Cellular Responses by PAF
II. Involvement of PAF in Allergic Reactions
C. Involvement of PAF in Cardiovascular Diseases
I. PAF in Vascular Disturbances
II. PAF in Endotoxin-Induced Shock
III. Thrombovascular Diseases
IV. Myocardial Infarction and Stroke
D. Involvement of PAF in Cerebral Disturbances
E. PAF in Respiratory Diseases
I. Bronchial Hyperresponsiveness
II. PAF in Asthma Bronchiale
III. Pulmonary Edema
IV. Adult Respiratory Distress Syndrome (ARDS)
V. Lung Fibrosis
F. Involvement of PAF in Gastrointestinal Diseases
I. Gastric Diseases
II. Intestinal Diseases
G. Involvement of PAF in Function and Disturbances of Reproduction
I. Ovulation
II. Gametocytes (Oocytes, Sperm)
III. Fertilization
IV. Oviduct Passage and Preimplantation State
V. Nidation
VI. Embryonic Development
H. Involvement of PAF in Skin Diseases
I. Involvement of PAF in Diseases of Other Organs
I. Renal Diseases
II. Hepatic Disturbances
III. Acute Pancreatitis
IV. Transplant Rejection
V. Tumor Growth
J. Conclusion
- References
29 Therapeutic Aspects of Platelet Pharmacology
- Aspirin
- Selective Thromboxane Blockade
- Ticlopidine and Clopidogrel
- Fibrinogen Receptor Antagonism
- References
I. The Glycoprotein IIb-IIIa Complex
II. Adhesive Ligands of the GPIIb-IIIa Complex
III. Redistribution of the GpIIb-IIIa Complex and Internalization of the Ligands
C. Platelet Aggregation Testing
I. Sample Preparation
II. Optical Aggregometry
III. Lumi-aggregometry
IV. Determination of Platelet Aggregation by Particle Counting 90
V. Potential and Limitations of Platelet Aggregation Testing
D. Inhibition of Platelet Aggregation as a Therapeutic Principle
E. Conclusions
- References
Section II: Platelet Biochemistry, Signal Transduction
5 Platelet Receptors: The Thrombin Receptor
A. Introduction
B. The Seven-Transmembrane Domain Receptor
I. Structure and Activation Mechanism
II. Receptor Desensitization and Resensitization
C. Glycoprotein Ib
D. Receptor Signaling and Platelet Responses
E. Thrombin Receptor Inhibitors
- References
6 Platelet ADP/Purinergic Receptors
A. Introduction
B. Platelet Responses to ADP
I. Platelet Functions
1. Shape Change
2. Binding of Fibrinogen
3. ADP-Induced Platelet Aggregation
4. Desensitization
II. Signal Transduction
1. Changes in Cytosolic Free Calcium Concentration
2. Changes in Inositol Phospholipids
3. Inhibition of Adenylyl Cyclase
4. Involvement of G Proteins
C. Platelet ADP Receptors
I. Binding Studies
II. ADP-Binding Proteins
III. The P2 Purinoceptor Family
IV. Current Hypothesis of a Two-Receptor Model
V. Future Perspectives
D. Conclusions
- References
7 Platelet Prostaglandin Receptors
A. Introduction
B. Thromboxane A2 Receptor
I. Structure and Ligand Binding Specificity
II. Signal Transduction
III. Regulation
C. Prostacyclin Receptor
I. Structure and Ligand Binding Specificity
II. Signal Transduction
III. Regulation
D. Prostaglandin D Receptor
I. Structure
II. Ligand Binding Specificity and Signal Transduction
E. Prostaglandin E Receptor Subtype; the EP3 Receptor
- References
8 Platelet Adhesion and Aggregation Receptors
A. Introduction
B. Platelet Surface Glycoproteins
C. The Glycoprotein Ib-V-IX Complex
I. Introduction
1. Glycoprotein Ib?
2. Glycoprotein Ib?
3. Glycoprotein IX
4. Glycoprotein V
5. Polymorphism Within GPIb?
II. Function of the Glycoprotein Ib-V-IX Complex
1. Bleeding Disorders
a) Bernard-Soulier Syndrome
b) Platelet-Type von Willebrand's Disease
2. GPIb-vWf Binding
3. Non-physiological Activators of the GPIb/vWF Axis
III. Expression of GPIb-V-IX
D. GPIIb-IIIa
E. GPIa-IIa
F. GPIc-IIa
G. GPIc'-IIa
H. CD36 (GPIIIb or GPIV)
I. P-selectin (CD62, GMP-140, PADGEM)
J. PECAM-1 (CD31)
K. Inhibition of Platelet Adhesion/Aggregation as a Prophylactic Tool or for Treatment of Acute Thrombotic Events
- References
9 Platelet G Proteins and Adenylyl and Guanylyl Cyclases
A. Introduction
B. G Proteins
I. General Considerations
1. Activation of G Proteins
2. Diversity of G Proteins
3. Structure of G Proteins
4. Co- and Posttranslational Modifications of Platelet G Proteins
II. G Proteins Expressed in Platelets
III. G Proteins as Modulators of Platelet Activation
1. Platelet-Activating G Proteins
2. Platelet-Inhibiting G Proteins
C. Adenylyl Cyclases
D. Guanylyl Cyclases
I. Membrane-Bound Guanylyl Cyclases
II. Soluble Guanylyl Cyclases
1. Regulation of Soluble Guanylyl Cyclases
2. Biosynthesis of Nitric Oxide
III. cGMP Receptor Proteins
1. cGMP-Dependent Protein Kinases
2. cGMP-Gated Channels
E. Physiological Role of Cyclic Nucleotides in Platelets
I. cGMP-Formation in Platelets
II. cGMP- and cAMP-Dependent Protein Kinases in Platelets
III. Substrates for cAMP- and cGMP-Dependent Protein Kinases in Platelets
IV. Cellular Responses Leading to Platelet Inhibition
- References
10 Platelet Phosphodiesterases
A. Introduction
B. Catalytic and Regulatory Properties of Human Platelet Phosphodiesterases
I. cGMP-Stimulated Phosphodiesterase
II. cGMP-Inhibited Phosphodiesterase
III. cGMP-Specific Phosphodiesterase
C. Synergistic Inhibition of Platelet Function by Cyclic Nucleotide Elevating Agents
D. Regulation of Platelet Phosphodiesterases by Insulin
E. Effect of Phosphodiesterase Inhibitors on Platelet Function
I. General Aspects
II. Specificity
F. Concluding Remarks
- References
11 Platelet Phospholipases C and D
A. Introduction
B. Receptor-Mediated Activation of Phosphoinositide-Specific Phospholipase C
I. Activation of Phosphoinositide-Specific Phospholipase C in Platelets
II. Formation of Second Messengers
1. Inositol 1,4,5-trisphosphate
2. 1,2-Diacylglycerol
3. Phosphatidic Acid and Lysophosphatidic Acid
III. Modulation of Phosphoinositide-Specific Phospholipase C
C. Regulation of Phosphoinositide-Specific Phospholipase C
I. Multiplicity of Phosphoinositide-Specific Phospholipase C
II. G-Protein-Mediated Phospholipase C-? Activation
III. Tyrosine Kinase-Mediated Phospholipase C-?Activation
D. Roles and Regulation of Phospholipase D in Platelet Activation
I. Activation of Phospholipase D in Platelets
II. Regulation of Phospholipase D Activity
E. Remarks
- References
12 Protein Kinase C and Its Interactions with Other Serine-Threonine Kinases
A. Introduction and Definition
B. Molecular Structure and Heterogeneity
C. PKC Activation by Lipid Mediators in Platelets
D. PKC Substrates, Binding Proteins, and Translocation
E. Functional Roles for PKC in Platelets
F. Relation of PKC Activation to Other Platelet Serine-Threonine Kinases and Their Effectors
G. Abnormalities of Platelet PKC in Disease
H. Summary and Future Areas of Research
- References
13 Platelet Protein Tyrosine Kinases
A. Background
B. Protein Tyrosine Kinases in Platelets
I. Src Family Kinases
1. Src
2. Other Src Family Members
II. Syk
III. JAK Family Kinases
IV. Focal Adhesion Kinase (FAK)
V. Receptor Protein Tyrosine Kinases
C. Potential Roles of Protein Tyrosine Kinases in Platelet Functions
I. Second Messenger Pathways
1. Phospholipases
2. Phosphoinositide 3-Kinase
3. GTP-Binding Proteins
4. Calcium
5. Cyclic Nucleotides
II. Platelet Responses
1. Shape Change
2. Aggregation
3. Adhesion
- References
14 Protein Phosphatases in Platelet Function
A. Introduction
B. Protein Serine/Threonine Phosphatases in Platelets
I. Classification of Serine/Threonine Protein Phosphatases
II. Inhibitors of Protein Serine/Threonine Phosphatases
III. The Presence of Protein Serine/Threonine Phosphatases in Platelets
IV. Effect of Okadaic Acid and Calyculin A in Platelets
V. Dephosphorylation of Cofilin in Platelets
VI. Protein Serine/Threonine Phosphatases in Platelets: Concluding Remarks
C. Protein Tyrosine Phosphatases
I. Classification of Protein Tyrosine Phosphatases
II. Distribution of Protein Tyrosine Phosphatases in Platelets
III. Regulation of Tyrosine Phosphorylation by Irreversible Platelet Aggregation
IV. Effect of Vanadate and Its Derivatives in Platelets
V. Effect of Phenylarsine Oxide in Platelets
VI. Possible Role of Protein Tyrosine Phosphatases in Ca2+ Entry
VII. Regulation of Protein Tyrosine Phosphatases by Serine/Threonine Phosphorylation
VIII. Protein Tyrosine Phosphatases in Platelets: Concluding Remarks
D. Dual Specificity Protein Phosphatases
E. Concluding Remarks
- References
15 Ca2+ Homeostasis in Human Platelets
A. Introduction
I. Ca2+ Homeostasis
B. Maintenance of Low Cytosolic Ca2+ Concentrations
I. Platelet SERCAs
II. Membrane Organisation, Properties and Regulation of Platelet SERCAs
III. Organellar Distribution of Platelet SERCA Pumps
IV. Plasma Membrane Calcium ATPases
V. Platelet PMCAs
VI. Na+/Ca2+ Exchanger
C. Mechanisms of Ca2+ Elevation in Platelets
I. Ca2+ Release from Intracellular Stores
1. Inositol (1,4,5) Trisphosphate
2. General Properties of IP3Rs
3. Platelet IP3Rs
4. In(1,4,5)P3-Induced Ca2+ Release from Platelet Intracellular Stores
II. Nature of Ca2+ Release from Intracellular Stores
III. Ca2+ Oscillations in Platelets
IV. Ca2+ Influx Mechanisms
V. Capacitative or Store-Regulated Ca2+ Entry
VI. Possible Direct Involvement of Second Messengers in Ca2+ Entry
VII. Integrin-Associated Plasma Membrane Ca2+ Flux
VIII. Ca2+ Influx Via Receptor-Operated Ca2+ Channel (ROC)
IX. Cyclic Nucleotide Effects on Ca2+ Influx
- References
16 Regulation of Platelet Function by Nitric Oxide and Other Nitrogen- and Oxygen-Derived Reactive Species
A. Introduction
B. A Historical Perspective
C. Nitric Oxide Synthase Isoenzymes
I. General Characteristics
II. Platelet Nitric Oxide Synthase
III. The Endothelial NOS
IV. Nitric Oxide Synthase Reaction
V. Metabolic Fate of NO
VI. Interactions of NO with Biomolecules
VII. Nitric Oxide - Physiological Regulator of Platelet Function
VIII. Role of NO in the Pathogenesis of Vascular Disorders
IX. Pharmacological Regulation of Platelet Function by NO Gas and NO Donor Drugs
D. Other Oxygen- and Nitrogen-Derived Reactive Species
I. Mechanisms of Action of Oxygen-Derived Radicals on Platelets
1. Thromboxane Generation
2. Cyclic Nucleotides
3. Stimulation of Platelet Serotonin Transport
4. Activation of Platelet Receptors
5. Formation of Nitric Oxide Donors
E. Conclusions
- References
17 Platelet 5-Hydroxytryptamine Transporters
A. Introduction
B. The Plasma Membrane 5-Hydroxytryptamine Transporter (SERT)
I. Ionic Requirements
1. Coupling to Na+
2. Coupling to Cl-
3. Coupling to K+
II. Reversal of Transport
III. Mechanism
IV. Purification
V. Cloning
VI. Regulation
C. Dense Granule Membrane Vesicles
I. Driving Forces
II. Purification
III. Cloning
- References
Section III: Platelet-Derived Factors
18 Dense Granule Factors
A. Introduction
B. Contents of Platelets
I. Nucleotides
II. Divalent Cations
III. Amines
IV. Other
C. Storage Mechanisms
D. Species Differences
E. Membrane Proteins
F. Discussion and Comments
- References
19 Protein Granule Factors
A. Introduction
B. Platelet Proteins
C. Platelet-Derived Growth Factors
D. Thrombospondin
E. Proteins Similar or Identical to Plasma Proteins
F. Enzymes
G. Summary and Conclusions
- References
20 Lysosomal Storage
A. Introduction
I. Lysosomes in General
II. Platelet Lysosomes
B. Lysosomal Hydrolases in Platelets
I. Glycosidases
1. Secretion
2. Subcellular Localization
II. Proteinases
III. Phospholipases
IV. Other
C. Lysosomal Membrane Proteins
D. Discussion and Comments
- References
21 Thromboxane A2 and Other Eicosanoids
A. Introduction
B. Platelet Arachidonic Acid Metabolism
I. Metabolites
II. Sources of Arachidonic Acid
III. Release of Arachidonic Acid
1. Phospholipase A2
2. Other Routes of Arachidonic Acid Liberation
C. Eicosanoids Affecting Platelet Function
I. Thromboxane A2
1. Introduction
a) Thromboxane A2 Receptors
b) Signal Transduction
- Intracellular Calcium
- Alkalinization of Intraplatelet pH
- Protein Kinase C Activation
- Tyrosine Phosphorylation
- Myosin Light Chain Kinase
II. Prostacyclin (PGI2, Epoprostanol)
III. 8-Epi-prostaglandin F2?
IV. Prostaglandin D2 (PGD2)
V. 12-Hete (12-Hydroxyeicosatetraenoic Acid)
D. Alterations in Thromboxane A2 Synthesis in Disease States
I. Diabetes Mellitus
II. Acute Coronary Artery Syndromes
III. Pregnancy-Induced Hypertension
IV. Cerebral Ischemia
V. Homocystinuria
VI. Sickle Cell Disease
VII. Effects of Fish Oils
E. Alterations in Thromboxane A2 Receptors in Disease States
I. Acute Coronary Artery Syndromes
II. Pregnancy-Induced Hypertension
III. Diabetes Mellitus
IV. Regulation by Androgenic Steroids
F. Aspirin, Thromboxane Synthase Inhibitors, and Thromboxane A2 Receptor Antagonists in Coronary Artery Disease
- References
22 Platelet-Activating Factor: Biosynthesis, Biodegradation, Actions
A. Introduction
B. Biosynthesis of PAF in Mammalian Cells
C. Catabolism of PAF in Mammalian Cells
D. PAF and Bacteria
E. PAF and Yeast Cells, Protozoans, Amoebas, and Parasites
F. Effects of PAF on Cell Proliferation
G. Some Effects of PAF on Several Cell Functions and Tissue Structures
H. Conclusion
- References
23 Qualitative and Quantitative Assessment of Platelet Activating Factors
A. PAF Molecular Diversity
B. Estimation of PAF Activity by Bioassay
I. Platelet Bioassay
1. Rabbit Platelet Bioassay
2. Platelet Desensitization
3. PAF Carriers in Platelet Bioassay
4. PAF Molecular Diversity in Platelet Bioassay
II. Other
C. Estimation of PAF Activity by Radioimmunoassay (RIA)
I. RIA Development and Use
II. PAF Molecular Diversity in RIA
D. Estimation of PAF by Radioreceptor Assay
E. Estimation of PAF Based on [3H]Acetate Incorporation
F. Analysis of PAF by Mass Spectrometry
I. Analysis of Intact PAF
II. Analysis of PAF After Derivatization
G. Concluding Comments
- References
24 Biosynthetic Inhibitors and Receptor Antagonists to Platelet Activating Factor
A. PAF: Historical Perspective and Pathology
B. Biosynthesis Inhibitors
I. Phospholipase PLA2 Inhibitors
II. Lyso-PAF-Transferase Inhibitors
C. Preclinical and Clinical PAF Receptor Antagonists
I. Abbott Laboratories
II. Alter S.A
III. Boehringer Ingelheim KG
IV. British Biotechnology Ltd
V. Eisai Co., Ltd
VI. Fujisawa Pharmaceutical Co
VII. Hoffmann-La Roche and Co., Ltd
VIII. Leo Pharmaceutical Products Ltd
IX. Merck Sharp and Dohme Research Laboratories
X. Ono Pharmaceutical Co., Ltd
XI. Pfizer Laboratories
XII. Rhône-Poulenc Santé Laboratories
XIII. Sandoz Research Institute
XIV. Sanofi Research
XV. Schering-Plough Research Institute
XVI. Solvay Pharma Laboratories
XVII. Sumitomo Pharmaceuticals Co., Ltd
XVIII. Takeda Chemical Co., Ltd
XIX. Uriach S.A
XX. Yamanouchi Pharmaceutical Company
XXI. Yoshitomi Pharmaceutical Industries Ltd
D. Conclusions
- References
Section IV: Clinical Aspects of Platelets and Their Factors
25 Platelets and the Vascular System: Atherosclerosis, Thrombosis, Myocardial Infarction
A. Introduction
B. Atherosclerosis
C. Thrombosis
D. Myocardial Infarction
E. Methodology of Radiolabeling of Platelets
F. Studies with Radiolabeled Platelets
I. Platelet Kinetics
II. Imaging
1. Atherosclerosis
2. Thrombosis
3. Myocardial Infarction
G. Platelet Aggregation
H. Conclusions
- References
26 Platelets, Vessel Wall, and the Coagulation System
A. Platelet-Endothelium Interaction
I. Role of Platelets in Maintaining Vascular Integrity
II. Control of Platelet Reactivity by Endothelial Cells
1. 13-Hydroxy-octadecadienoic Acid (13-HODE) - An Antiadhesive Fatty Acid Metabolite
2. Endothelium-Derived Platelet Inhibitors
3. Platelet Effects on PGI2 and EDRF/NO Synthesis
4. Mechanisms of Platelet Inhibition by PGI2 and EDRF/NO
5. Endothelial-Bound Antiplatelet Factors
6. Platelet Adhesion to Endothelial Cells
III. Platelet-Mediated Inflammatory and Procoagulant Alterations of Endothelial Cells
B. Platelets and Coagulation
I. Membrane-Dependent Reactions in Blood Coagulation
II. Platelet Procoagulant Activity
III. Mechanisms Involved in the Maintenance of Membrane Lipid Asymmetry
IV. Mechanisms Involved in the Expression of Procoagulant Activity
V. Platelet Microvesicles
VI. Platelets and Coagulation Disorders
1. Scott Syndrome
2. Antiphospholipid Syndrome
3. Factor V Quebec
VII. Anticoagulant Activities of Platelets and Microvesicles
VIII. Role of Platelets in Fibrinolysis
- References
27 Platelet Flow Cytometry - Adhesive Proteins
A. Introduction
I. Procedures for the Diagnosis of Platelet Disease States
1. Problems
2. Requirements
B. Single Platelet Flow Cytometry (SPFC)
I. Principle
II. Pitfalls and Standardization Requirements
III. Assay Systems
C. Platelet Adhesion Molecules as Diagnostic Targets
I. Megakaryocytic Conditioning
II. Platelet Membrane Processing
III. Defining Diagnostic Epitopes
1. The Constitutive Stain
2. The Functional Stain
IV. Platelet-Leukocyte Coaggregates
D. Applications in Platelet Pathology
I. Hemorrhagic Diathesis
II. Thrombotic Diathesis
III. Inflammation
E. Pharmacology
- References
28 Pathological Aspects of Platelet-Activating Factor (PAF)
A. Introduction
B. Involvement of PAF in Inflammatory and Allergic Responses
I. Inflammatory Cellular Responses by PAF
II. Involvement of PAF in Allergic Reactions
C. Involvement of PAF in Cardiovascular Diseases
I. PAF in Vascular Disturbances
II. PAF in Endotoxin-Induced Shock
III. Thrombovascular Diseases
IV. Myocardial Infarction and Stroke
D. Involvement of PAF in Cerebral Disturbances
E. PAF in Respiratory Diseases
I. Bronchial Hyperresponsiveness
II. PAF in Asthma Bronchiale
III. Pulmonary Edema
IV. Adult Respiratory Distress Syndrome (ARDS)
V. Lung Fibrosis
F. Involvement of PAF in Gastrointestinal Diseases
I. Gastric Diseases
II. Intestinal Diseases
G. Involvement of PAF in Function and Disturbances of Reproduction
I. Ovulation
II. Gametocytes (Oocytes, Sperm)
III. Fertilization
IV. Oviduct Passage and Preimplantation State
V. Nidation
VI. Embryonic Development
H. Involvement of PAF in Skin Diseases
I. Involvement of PAF in Diseases of Other Organs
I. Renal Diseases
II. Hepatic Disturbances
III. Acute Pancreatitis
IV. Transplant Rejection
V. Tumor Growth
J. Conclusion
- References
29 Therapeutic Aspects of Platelet Pharmacology
- Aspirin
- Selective Thromboxane Blockade
- Ticlopidine and Clopidogrel
- Fibrinogen Receptor Antagonism
- References
... weniger
Bibliographische Angaben
- 2011, Softcover reprint of the original 1st ed. 1997, XXVIII, 753 Seiten, 753 farbige Abbildungen, Maße: 15,5 x 23,5 cm, Kartoniert (TB), Englisch
- Herausgegeben: Franz von Bruchhausen, Ulrich Walter
- Verlag: Springer, Berlin
- ISBN-10: 3642644880
- ISBN-13: 9783642644887
Sprache:
Englisch
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