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I organized this book because there is a need to put together in book form recent advances in our knowledge of how airway smooth muscle:works in health and in disease. After a period when it seemed that progress was very slow, there has been in the past few years an incredibly rapid gathering of knowledge in this area. In particular, our understanding has improved regarding the cascades of events that follow the initial binding of agonist to plasma membrane receptors and that lead to the cross-bridge movements that determine contraction. This advance in our knowledge was stimulated by use of…mehr
I organized this book because there is a need to put together in book form recent advances in our knowledge of how airway smooth muscle:works in health and in disease. After a period when it seemed that progress was very slow, there has been in the past few years an incredibly rapid gathering of knowledge in this area. In particular, our understanding has improved regarding the cascades of events that follow the initial binding of agonist to plasma membrane receptors and that lead to the cross-bridge movements that determine contraction. This advance in our knowledge was stimulated by use of single-and whole-cell channel recordings of plasma membrane currents and by description of the l3-receptor-GTP-binding protein-adenylate cyclase-cAMP coupling system, which serves as a model for other coupling mechanisms. The discovery of the receptor-activated inositol phospholipid transduction system has greatly stimulated research and led to advances in our understanding of mechanisms involved in smooth muscle con traction. Major advances were also triggered by the development of indicators for measuring free cytosolic calcium concentration and starting the unraveling of 2 the events involved in Ca + -dependent activation of contractile proteins. Al though most of the studies that led to our current understanding of these areas were performed on nonairway smooth muscle, these studies usually add to our understanding of airway smooth muscle, and there is an enlarging body of data that have been obtained on airway smooth muscle.
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1 Structure of Airway Smooth Muscle and Its Innervation.- I. Nerve Supply to Trachea and Bronchi.- II. Structure of the Musculature.- III. Nerve-Mediated Responses.- IV. Distribution of Intramuscular Nerves.- V. Histochemical Types of Nerve Fibers.- VI. Density of Innervation.- VII. Types of Nerve Endings.- VIII. Neuromuscular Junctions.- IX. Smooth Muscle Cells.- X. Gap Junctions.- XI. References.- 2 Integration of Neural Inputs in Peripheral Airway Ganglia.- I. Introduction.- II. Neural Input to Airway Smooth Muscle: How the System Is Wired.- III. Basic Properties of Peripheral Airway Ganglia.- IV. Circuitry of Ferret Paratracheal Ganglion Neurons.- V. Integration and Modulation of Neural Inputs.- A. Peripheral Airway Ganglia.- B. Neuromuscular Junction.- VI. References.- 3 Nervous Receptors in the Tracheobronchial Tree: Airway Smooth Muscle Reflexes.- I. Introduction.- II. Pulmonary Stretch Receptors.- A. Reflex Actions on Airway Smooth Muscle.- B. Other Reflex Actions.- III. Rapidly Adapting (Irritant) Receptors.- A. Reflex Actions on Airway Smooth Muscle.- B. Other Reflex Actions.- IV. C-Fiber Receptors.- A. Reflex Actions on Airway Smooth Muscle.- B. Other Reflex Actions.- V. Local (Axon) Reflex Actions.- VI. Neuroepithelial Bodies.- VII. Other Reflex Actions on Airway Smooth Muscle.- A. Reflexes from the Upper Respiratory Tract.- B. Bronchomotor Reflexes from Other Sites.- VIII. Motor Pathways to Tracheobronchial Smooth Muscle.- IX. References.- 4 Polypeptide-Containing Neurons and Their Function in Airway Smooth Muscle.- I. Neuropeptides as Physiological Regulators.- II. Autonomic Innervation of Airways: Peptidergic Neurons.- III. Identification, Localization, and Distribution of Peptidergic Neurons.- IV. Families of Neuropeptides.- V. Peptides as Neurotransmitters and Neuromodulators.- A. When Are Neuropeptides Neurotransmitters?.- B. Neurotransmitter versus Endocrine and Paracrine Secretions.- C. Coexistence of Peptides and Other Neurotransmitters.- D. How Neuropeptides May Influence Respiratory Function.- E. Bronchoactive Peptides.- F. Interactions between Neuropeptides and Classic Neurotransmitters.- VI. Neuropeptide Receptors on Smooth Muscle.- A. VIP and PHI/PHM.- B. Substance P and Other Neurokinins.- C. Atrial Natriuretic Peptide.- VII. Mechanisms of Bronchial Relaxation and Constriction by Neuropeptides.- VIII. Importance of Airway Epithelium in Responses to Bronchoactive Agents.- IX. Neuropeptides as Physiological Regulators of Airway Smooth Muscle Function.- A. VIP.- B. Substance P and Other Neurokinins.- X. Regulating the Regulators: Enzymatic Degradation of Airway Peptides.- XI. Neuropeptides in Airway Disease.- A. VIP in the Pathogenesis of Airway Disease.- B. Neurokinins P and Other Sensory Neuropeptides.- XII. Conclusion.- XIII. References.- 5 Cell-Surface Receptors in Airway Smooth Muscle.- I. Introduction.- II. Indirect Regulation of Airway Smooth Muscle.- III. Airway Receptors and Disease.- IV. Autonomic Receptors.- A. Autonomic Control of Airways.- B. ?-Adrenoceptors.- C. ?-Receptor Subtypes.- D. ?-Receptor Dysfunction in Asthma.- E. ?-Adrenoceptors.- F. ?-Receptor Subtypes.- G. ?-Receptors in Asthma.- H. Cholinergic Receptors.- I. Muscarinic Receptor Subtypes.- V. Neuropeptide Receptors.- A. VIP Receptors.- B. Tachykinin Receptors.- C. Other Neuropeptide Receptors.- VI. Mediator Receptors.- A. Histamine Receptors.- B. Prostanoid Receptors.- C. Leukotriene Receptors.- D. Platelet Activating Factor Receptors.- E. Adenosine Receptors.- F. Bradykinin Receptors.- VII. Conclusions.- VIII. References.- 6Cellular Control Mechanisms in Airway Smooth Muscle.- I. Introduction.- II. Biochemistry of Smooth Muscle Contraction.- III. Physiological Experiments on Myosin Phosphorylation.- IV. Other Possible Regulatory Mechanisms.- V. Cyclic Nucleotide Effects.- VI. Myosin Phosphorylation by Other Protein Kinases.- VII. Myosin Phosphatases.- VIII. Summary.- IX. References.- 7 Transduction and Signaling in Airway Smooth Muscle.- I. Introduction.- II. Control of Second-Messenger Production by Guanine Nucleotide-Binding Proteins.- III. Inositol Phospholipid Metabolism.- A. Hydrolysis of PI-4,5-P2 by Inositol Phospholipid-Specific Phospholipase C and Ca2+ Release.- B. Formation of Diacylglycerol, Activation of Protein Kinase C, and Modulation of PI-4,5-P2 Hydrolysis.- C. Metabolism of Inositol Phosphates.- D. Synthesis of Phosphatidylinositol.- E. Rates of Synthesis of Inositol Phospholipids.- F. Compartmentation of Inositol Phospholipids.- G. Other Reactions of Inositol Phospholipid Metabolism.- H. ATP Utilization by Inositol Phospholipid Metabolism.- I. Considerations for Labeling Methods in Assessment of Inositol Phospholipid Metabolism.- IV. Stale of Knowledge in Airway Smooth Muscle.- V. Summary.- VI. References.- 8 Electrical Properties of Airway Smooth Muscle.- I. Introduction.- II. Technical Problems.- III. Membrane Potential and Spontaneous Electrical Activity.- IV. Evoked Action Potentials.- V. Response to Excitatory Agents.- VI. Response to Inhibitory Agents.- VII. Summary.- VIII. References.- 9 Ion Channels in Airway Smooth Muscle.- I. Introduction.- II. Ion Channels.- III. Patch-Clamp Techniques.- IV. Potassium Channels in Airway Smooth Muscle.- V. Calcium Channels in Airway Smooth Muscle.- VI. Functional Characteristics of Ion Channels in Airway Smooth Muscle.- VII. References.- 10 Coupling Mechanisms in Airway Smooth Muscle.- I. Introduction.- II. Pharmacomechanical Coupling Mechanisms.- III. Electromechanical Coupling Mechanisms during Muscarinic Contractions.- IV. Coupling between Receptors, Channels, and Second-Messenger Systems.- V. Cytosolic Free Calcium Concentration.- VI. Modulation of Electromechanical and Pharmacomechanical Coupling Mechanisms.- VII. Summary.- VIII. References.- 11 Postulated Mechanisms Underlying Airway Hyperreactivity: Relationship to Supersensitivity.- I. Introduction.- II. Potential Mechanisms of Airway Hyperreactivity.- A. Dysfunction in Receptors.- B. Imbalance in Regulation of the Autonomic Nervous System.- C. Change in Electrophysiological Characteristics of Smooth Muscle Cells.- D. Abnormalities in Ca2+ Translocation and Handling.- E. Change in Airway Morphology/Geometry: Mechanical Factors.- F. Decreased Airway Caliber.- G. Increased Release of Mediators.- H. Epithelial Cell Damage or Dysfunction.- III. Inflammation.- IV. Summary.- V. References.- 12 Airway Epithelial Metabolism and Airway Smooth Muscle Hyperresponsiveness.- I. Introduction.- II. Epithelial Permeability.- III. Epithelial Mediator Release.- IV. Airway Inflammation.- A. Neutrophils.- B. Monocytes/Macrophages.- C. Mast Cells.- D. Eosinophils.- E. Platelets.- V. Viral Infection of Airway Epithelium.- A. Induction of Airway Inflammation.- B. Damage to Airway Epithelium.- C. Impaired ?-Adrenoceptor Function.- D. Induction of IgE Response.- E. Increased Release of Histamine by Mast Cells.- F. Induction of T-Lymphocyte Response.- G. Increased Sensitivity to the Bronchoconstncting Effects of Substance P.- VI. Sensory Nerve Products.- VII. Summary.- VIII. References.- 13 Airway Hyperreactivity: Relationship to Disease States.- I.Introduction.- II. Graded Dose-Response Curve.- III. Smooth Muscle Activation.- IV. Smooth Muscle Contraction.- V. Wall Thickness and Secretions.- VI. Summary.- VII. References.- 14 Current Concepts of the Pathophysiology of Allergic Asthma.- I. Introduction.- II. Allergic Asthma.- A. Diagnosis.- B. Epidemiology.- C. Natural History, Morbidity, and Mortality.- D. Inheritance.- III. Pathophysiology of Allergic Asthma.- A. Antigen Entry.- B. Pulmonary Mast Cells.- C. Mast Cell Stimulation and Mediator Release.- IV. Pathological Processes in Allergic Asthma.- A. Bronchospasm.- B. Mucosal Edema.- C. Mucus Secretion.- D. Late-Phase Reactions.- E. Desquamation of Surface Epithelium, Thickening of the Basement Membrane, and Goblet Cell Hyperplasia.- V. Airway Inflammation and Hyperreactivity.- VI. Other Modulators of Airway Responsiveness.- VII. Summary.- VIII. References.- 15 Exercise-Induced Bronchoconstriction.- I. Definition of Exercise-Induced Bronchoconstriction.- A. Response of Normal Subjects to Exercise.- B. Clinical Presentation of Exercise-Induced Bronchoconstriction.- II. Mechanism of Exercise-Induced Bronchoconstriction.- A. Heat and Water Exchange in Upper Airways.- B. Role of Minute Ventilation.- C. Consequence of Heat Loss and Water Loss.- III. Summary.- IV. References.
1 Structure of Airway Smooth Muscle and Its Innervation.- I. Nerve Supply to Trachea and Bronchi.- II. Structure of the Musculature.- III. Nerve-Mediated Responses.- IV. Distribution of Intramuscular Nerves.- V. Histochemical Types of Nerve Fibers.- VI. Density of Innervation.- VII. Types of Nerve Endings.- VIII. Neuromuscular Junctions.- IX. Smooth Muscle Cells.- X. Gap Junctions.- XI. References.- 2 Integration of Neural Inputs in Peripheral Airway Ganglia.- I. Introduction.- II. Neural Input to Airway Smooth Muscle: How the System Is Wired.- III. Basic Properties of Peripheral Airway Ganglia.- IV. Circuitry of Ferret Paratracheal Ganglion Neurons.- V. Integration and Modulation of Neural Inputs.- A. Peripheral Airway Ganglia.- B. Neuromuscular Junction.- VI. References.- 3 Nervous Receptors in the Tracheobronchial Tree: Airway Smooth Muscle Reflexes.- I. Introduction.- II. Pulmonary Stretch Receptors.- A. Reflex Actions on Airway Smooth Muscle.- B. Other Reflex Actions.- III. Rapidly Adapting (Irritant) Receptors.- A. Reflex Actions on Airway Smooth Muscle.- B. Other Reflex Actions.- IV. C-Fiber Receptors.- A. Reflex Actions on Airway Smooth Muscle.- B. Other Reflex Actions.- V. Local (Axon) Reflex Actions.- VI. Neuroepithelial Bodies.- VII. Other Reflex Actions on Airway Smooth Muscle.- A. Reflexes from the Upper Respiratory Tract.- B. Bronchomotor Reflexes from Other Sites.- VIII. Motor Pathways to Tracheobronchial Smooth Muscle.- IX. References.- 4 Polypeptide-Containing Neurons and Their Function in Airway Smooth Muscle.- I. Neuropeptides as Physiological Regulators.- II. Autonomic Innervation of Airways: Peptidergic Neurons.- III. Identification, Localization, and Distribution of Peptidergic Neurons.- IV. Families of Neuropeptides.- V. Peptides as Neurotransmitters and Neuromodulators.- A. When Are Neuropeptides Neurotransmitters?.- B. Neurotransmitter versus Endocrine and Paracrine Secretions.- C. Coexistence of Peptides and Other Neurotransmitters.- D. How Neuropeptides May Influence Respiratory Function.- E. Bronchoactive Peptides.- F. Interactions between Neuropeptides and Classic Neurotransmitters.- VI. Neuropeptide Receptors on Smooth Muscle.- A. VIP and PHI/PHM.- B. Substance P and Other Neurokinins.- C. Atrial Natriuretic Peptide.- VII. Mechanisms of Bronchial Relaxation and Constriction by Neuropeptides.- VIII. Importance of Airway Epithelium in Responses to Bronchoactive Agents.- IX. Neuropeptides as Physiological Regulators of Airway Smooth Muscle Function.- A. VIP.- B. Substance P and Other Neurokinins.- X. Regulating the Regulators: Enzymatic Degradation of Airway Peptides.- XI. Neuropeptides in Airway Disease.- A. VIP in the Pathogenesis of Airway Disease.- B. Neurokinins P and Other Sensory Neuropeptides.- XII. Conclusion.- XIII. References.- 5 Cell-Surface Receptors in Airway Smooth Muscle.- I. Introduction.- II. Indirect Regulation of Airway Smooth Muscle.- III. Airway Receptors and Disease.- IV. Autonomic Receptors.- A. Autonomic Control of Airways.- B. ?-Adrenoceptors.- C. ?-Receptor Subtypes.- D. ?-Receptor Dysfunction in Asthma.- E. ?-Adrenoceptors.- F. ?-Receptor Subtypes.- G. ?-Receptors in Asthma.- H. Cholinergic Receptors.- I. Muscarinic Receptor Subtypes.- V. Neuropeptide Receptors.- A. VIP Receptors.- B. Tachykinin Receptors.- C. Other Neuropeptide Receptors.- VI. Mediator Receptors.- A. Histamine Receptors.- B. Prostanoid Receptors.- C. Leukotriene Receptors.- D. Platelet Activating Factor Receptors.- E. Adenosine Receptors.- F. Bradykinin Receptors.- VII. Conclusions.- VIII. References.- 6Cellular Control Mechanisms in Airway Smooth Muscle.- I. Introduction.- II. Biochemistry of Smooth Muscle Contraction.- III. Physiological Experiments on Myosin Phosphorylation.- IV. Other Possible Regulatory Mechanisms.- V. Cyclic Nucleotide Effects.- VI. Myosin Phosphorylation by Other Protein Kinases.- VII. Myosin Phosphatases.- VIII. Summary.- IX. References.- 7 Transduction and Signaling in Airway Smooth Muscle.- I. Introduction.- II. Control of Second-Messenger Production by Guanine Nucleotide-Binding Proteins.- III. Inositol Phospholipid Metabolism.- A. Hydrolysis of PI-4,5-P2 by Inositol Phospholipid-Specific Phospholipase C and Ca2+ Release.- B. Formation of Diacylglycerol, Activation of Protein Kinase C, and Modulation of PI-4,5-P2 Hydrolysis.- C. Metabolism of Inositol Phosphates.- D. Synthesis of Phosphatidylinositol.- E. Rates of Synthesis of Inositol Phospholipids.- F. Compartmentation of Inositol Phospholipids.- G. Other Reactions of Inositol Phospholipid Metabolism.- H. ATP Utilization by Inositol Phospholipid Metabolism.- I. Considerations for Labeling Methods in Assessment of Inositol Phospholipid Metabolism.- IV. Stale of Knowledge in Airway Smooth Muscle.- V. Summary.- VI. References.- 8 Electrical Properties of Airway Smooth Muscle.- I. Introduction.- II. Technical Problems.- III. Membrane Potential and Spontaneous Electrical Activity.- IV. Evoked Action Potentials.- V. Response to Excitatory Agents.- VI. Response to Inhibitory Agents.- VII. Summary.- VIII. References.- 9 Ion Channels in Airway Smooth Muscle.- I. Introduction.- II. Ion Channels.- III. Patch-Clamp Techniques.- IV. Potassium Channels in Airway Smooth Muscle.- V. Calcium Channels in Airway Smooth Muscle.- VI. Functional Characteristics of Ion Channels in Airway Smooth Muscle.- VII. References.- 10 Coupling Mechanisms in Airway Smooth Muscle.- I. Introduction.- II. Pharmacomechanical Coupling Mechanisms.- III. Electromechanical Coupling Mechanisms during Muscarinic Contractions.- IV. Coupling between Receptors, Channels, and Second-Messenger Systems.- V. Cytosolic Free Calcium Concentration.- VI. Modulation of Electromechanical and Pharmacomechanical Coupling Mechanisms.- VII. Summary.- VIII. References.- 11 Postulated Mechanisms Underlying Airway Hyperreactivity: Relationship to Supersensitivity.- I. Introduction.- II. Potential Mechanisms of Airway Hyperreactivity.- A. Dysfunction in Receptors.- B. Imbalance in Regulation of the Autonomic Nervous System.- C. Change in Electrophysiological Characteristics of Smooth Muscle Cells.- D. Abnormalities in Ca2+ Translocation and Handling.- E. Change in Airway Morphology/Geometry: Mechanical Factors.- F. Decreased Airway Caliber.- G. Increased Release of Mediators.- H. Epithelial Cell Damage or Dysfunction.- III. Inflammation.- IV. Summary.- V. References.- 12 Airway Epithelial Metabolism and Airway Smooth Muscle Hyperresponsiveness.- I. Introduction.- II. Epithelial Permeability.- III. Epithelial Mediator Release.- IV. Airway Inflammation.- A. Neutrophils.- B. Monocytes/Macrophages.- C. Mast Cells.- D. Eosinophils.- E. Platelets.- V. Viral Infection of Airway Epithelium.- A. Induction of Airway Inflammation.- B. Damage to Airway Epithelium.- C. Impaired ?-Adrenoceptor Function.- D. Induction of IgE Response.- E. Increased Release of Histamine by Mast Cells.- F. Induction of T-Lymphocyte Response.- G. Increased Sensitivity to the Bronchoconstncting Effects of Substance P.- VI. Sensory Nerve Products.- VII. Summary.- VIII. References.- 13 Airway Hyperreactivity: Relationship to Disease States.- I.Introduction.- II. Graded Dose-Response Curve.- III. Smooth Muscle Activation.- IV. Smooth Muscle Contraction.- V. Wall Thickness and Secretions.- VI. Summary.- VII. References.- 14 Current Concepts of the Pathophysiology of Allergic Asthma.- I. Introduction.- II. Allergic Asthma.- A. Diagnosis.- B. Epidemiology.- C. Natural History, Morbidity, and Mortality.- D. Inheritance.- III. Pathophysiology of Allergic Asthma.- A. Antigen Entry.- B. Pulmonary Mast Cells.- C. Mast Cell Stimulation and Mediator Release.- IV. Pathological Processes in Allergic Asthma.- A. Bronchospasm.- B. Mucosal Edema.- C. Mucus Secretion.- D. Late-Phase Reactions.- E. Desquamation of Surface Epithelium, Thickening of the Basement Membrane, and Goblet Cell Hyperplasia.- V. Airway Inflammation and Hyperreactivity.- VI. Other Modulators of Airway Responsiveness.- VII. Summary.- VIII. References.- 15 Exercise-Induced Bronchoconstriction.- I. Definition of Exercise-Induced Bronchoconstriction.- A. Response of Normal Subjects to Exercise.- B. Clinical Presentation of Exercise-Induced Bronchoconstriction.- II. Mechanism of Exercise-Induced Bronchoconstriction.- A. Heat and Water Exchange in Upper Airways.- B. Role of Minute Ventilation.- C. Consequence of Heat Loss and Water Loss.- III. Summary.- IV. References.
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