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Physiology of the Gastrointestinal Tract, Fifth Edition — winner of a 2013 Highly Commended BMA Medical Book Award for Internal Medicine — covers the study of the mechanica… Read more
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Immediately download your ebook while waiting for your print delivery. No promo code needed.
Physiology of the Gastrointestinal Tract, Fifth Edition — winner of a 2013 Highly Commended BMA Medical Book Award for Internal Medicine — covers the study of the mechanical, physical, and biochemical functions of the GI Tract while linking the clinical disease or disorder, bridging the gap between clinical and laboratory medicine.
The gastrointestinal system is responsible for the breakdown and absorption of various foods and liquids needed to sustain life. Other diseases and disorders treated by clinicians in this area include: food allergies, constipation, chronic liver disease and cirrhosis, gallstones, gastritis, GERD, hemorrhoids, IBS, lactose intolerance, pancreatic, appendicitis, celiac disease, Crohn’s disease, peptic ulcer, stomach ulcer, viral hepatitis, colorectal cancer and liver transplants.
The new edition is a highly referenced and useful resource for gastroenterologists, physiologists, internists, professional researchers, and instructors teaching courses for clinical and research students.
Clinical gastroenterologists, physiologists, and internists, as well as, professional researchers in gastroenterology, physiology, internal medicine, translational medicine and biomedicine.
Contributors
Preface to the First Edition
Preface
Acknowledgments
VOLUME 1
Section I Basic Cell Physiology, Genetics, and Growth of the GI Tract
Chapter 1. Transcription and Epigenetic Regulation
1.1 Overview of Gene Organization
1.2 Epigenetic Influences
1.3 Anatomy of a Gene Promoter
1.4 Methodology
1.5 Transcriptional Control of Gastrointestinal Peptides
1.6 Post-Transcriptional Processing
1.7 Transport Across the Nuclear Membrane
1.8 Concluding Remarks
Acknowledgments
References
Chapter 2. Post-translational Processing of Gastrointestinal Peptides
2.1 Introduction
2.2 Translation and Passage into the Endoplasmic Reticulum
2.3 Processing in the Endoplasmic Reticulum
2.4 Sorting to the Golgi
2.5 Processing in the Golgi
2.6 Sorting to the Secretory Vesicle
2.7 Processing in the Secretory Vesicle
2.8 Examples of Processing
2.9 Summary
References
Chapter 3. Genetic Tools in Gastrointestinal Diseases
3.1 The Genetic Architecture of Mendelian and Non-Mendelian Diseases
3.2 Genome-Wide Association Studies
3.3 DNA Sequencing and Disease Association Studies of Uncommon Variants
3.4 DNA-RNA Translation Mappings
3.5 Epigenetic Regulation of Gene Expression
3.6 Integrating Genetic and Environmental Factors
3.7 Clinical Applications
3.8 Future Directions
References
Chapter 4. Signaling Pathways Induced by G-protein-coupled Receptors
4.1 Introduction
4.2 GPCR Structure, Oligomerization, and Heterotrimeric G Proteins
4.3 GPCR Phosphorylation, Conformational Changes, Arrestin Recruitment, and G-Protein-Independent Signaling
4.4 GPCR-Induced Actin Remodeling and Phosphorylation of Focal Adhesion Proteins
4.5 GPCR-Induced Fak Phosphorylation at Tyrosine and Serine Residues
4.6 Signaling through Gs, cAMP, PKA, and EPAC
4.7 GPCR Signaling Leads to Cell Cycle Activation
4.8 Conclusions, Implications, and Emerging Themes
Acknowledgments
References
Chapter 5. Transgenic Animal Models of Gastrointestinal Function
5.1 Introduction
5.2 Generation of Transgenic Mice
5.3 Generation of Genetically Engineered Mice by Gene Targeting
5.4 Promoters Used to Study Gastrointestinal Functions
5.5 Genetic Mouse Models for Studies of Normal Gastrointestinal Function
5.6 Genetic Mouse Models of Gastrointestinal Diseases
5.7 Conclusion
References
Chapter 6. Gastrointestinal Peptides
6.1 General Overview
6.2 Gastrin
6.3 Cholecystokinin
6.4 Somatostatin
6.5 Ghrelin
6.6 Concluding Remarks
References
Chapter 7. Postpyloric Gastrointestinal Peptides
7.1 Secretin
7.2 Intestinal Somatostatin
7.3 Vasoactive Intestinal Polypeptide and Related Peptides
7.4 Neurotensin
7.5 Neuropeptide Y
7.6 Motilin
7.7 Peptide YY
7.8 Conclusions
References
Chapter 8. Growth Factors in the Gastrointestinal Tract
8.1 Introduction
8.2 TGF-β Family of Peptides and Receptors
8.3 Epidermal Growth Factor Family of Peptides and Receptors
8.4 Insulin-Like Growth Factors
8.5 Trefoil Factor Family of Peptides
8.6 Hepatocyte Growth Factor
8.7 Fibroblast Growth Factor Family
8.8 Hedgehog Family of Peptides
Acknowledgments
References
Chapter 9. Developmental Signaling Networks
9.1 Introduction
9.2 History
9.3 THE WNT/β-Catenin Pathway
9.4 Non-Canonical WNT Signaling Pathways
9.5 WNT/β-catenin Pathway in Gastrointestinal Physiology
9.6 WNT/β-catenin Pathway Defects in Gastrointestinal Tumors
9.7 Conclusion
References
Chapter 10. Hedgehog Signaling in Gastrointestinal Morphogenesis and Morphostasis
10.1 Patterning
10.2 The Hedgehog Pathway
10.3 The Role of Hh Signaling in the Developing Gut
10.4 Hh Signaling in Homeostasis of the Adult Gastrointestinal Tract
10.5 Hh Signaling and Carcinogenesis of the Gastrointestinal Tract
10.6 Conclusions and Future Perspectives
References
Chapter 11. Notch Pathway Regulation of Intestinal Cell Fate
11.1 Notch Pathway Overview
11.2 Regulation of Notch Pathway Components
11.3 Overview of Intestinal Structure and Development
11.4 Notch Signaling in Intestine
11.5 Notch Signaling and Intestinal Stem and Progenitor Cells
11.6 Cell Fate Specification
11.7 Notch and Human Disease
11.8 Concluding Remarks
References
Chapter 12. Stem Cells in the Gastrointestinal Tract
12.1 Intestinal Stem Cells
12.2 The Gastrointestinal Stem Cell Niche
12.3 Stem Cells in the Gastric Gland
12.4 Symmetric and Asymmetric Stem Cell Divisions
12.5 The Human Gastrointestinal Tract
12.6 Stem Cells in Repair and Regeneration
12.7 Conclusion
References
Chapter 13. Programmed Cell Death in the Gastrointestinal Tract
13.1 Cell Death
13.2 Intestinal Epithelia: In Vivo Studies
13.3 Intestinal Cells: In Vitro Studies
13.4 Gastric Mucosa
13.5 Concluding Remarks
References
Chapter 14. Molecular Physiology of Gastrointestinal Function during Development
14.1 Ontogeny of Secretory Function
14.2 Ontogeny of Digestive Function
14.3 Ontogeny of Intestinal Transport
14.4 Ontogeny of Transport Function Along the Vertical and Horizontal Gut Axes
14.5 Developmental Regulation of Gastrointestinal Function
14.6 Acknowledgments
References
Chapter 15. The Cell Cycle
15.1 Components of the Cell Cycle
15.2 Control of the Cell Cycle
15.3 Checkpoints
15.4 Pathological Consequences of Cell Cycle Deregulation or Dysregulation
15.5 Conclusion
Acknowledgment
References
Section II Neurogastroenterology
Chapter 16. Development of the Enteric Nervous System
16.1 Origin and Migratory Pathways of ENS Precursors
16.2 Cellular and Molecular Regulation of ENS Development
16.3 Development of Enteric Neuron Subtypes, Glial Cells, and Ganglia
16.4 Development of Neural Control of Motility
16.5 Conclusions
Acknowledgments
References
Chapter 17. Cellular Physiology of Gastrointestinal Smooth Muscle
17.1 Signal Transduction
17.2 Small Heat Shock Proteins
17.3 Thin Filament Regulation
17.4 Special Mechanisms
17.5 Summary
References
Chapter 18. Organization and Electrophysiology of Interstitial Cells of Cajal and Smooth Muscle Cells in the Gastrointestinal Tract
18.1 Electrical Activity in Gastrointestinal Muscles
18.2 Role of Interstitial Cells of Cajal in Spontaneous Electrical Rhythmicity
18.3 Role of Interstitial Cells of Cajal in Neurotransmission
18.4 Role of Interstitial Cells of Cajal as Stretch Receptors
18.5 Motility Disorders Associated with Loss of Interstitial Cells of Cajal
18.6 Animal Models to Study Loss of Interstitial Cells of Cajal
18.7 Smooth Muscle Responses to Slow Waves and Neural Inputs
18.8 Integration of Electrical Activity in Gastrointestinal Muscles
Acknowledgments
References
Chapter 19. Enteric Nervous System Structure and Neurochemistry Related to Function and Neuropathology
19.1 General Organization of the Enteric Nervous System
19.2 Neuronal Morphology
19.3 Morphological and Neurochemical Characteristics of Functionally Defined Neurons
19.4 Chemical Coding, Multiple Transmitters, and Species Variation and its Relevance
19.5 The Organization of Enteric Circuits
19.6 A Possible Explanation of the Functional Differences But Structural Similarities Between Regions
19.7 Enteric Neuropathies
19.8 Conclusions
Acknowledgments
References
Chapter 20. Physiology of Prevertebral Sympathetic Ganglia
20.1 Overview
20.2 General Properties of PVG Neurons
20.3 Reflexes Through Peripheral Ganglia
20.4 PVG and the Immune System
20.5 PVG and Inflammation
20.6 PVG Diabetes and Aging
20.7 Concluding Remarks
Acknowledgments
References
Chapter 21. Cellular Neurophysiology of Enteric Neurons
21.1 The Enteric Nervous System
21.2 AH- and S-Type Enteric Neurons
21.3 Synaptic Transmission
References
Chapter 22. Integrative Functions of the Enteric Nervous System
22.1 Enteric Nervous System
22.2 Integrated Control of the Stomach
22.3 Integrated Control of the Small and Large Intestine
22.4 Plasticity in the ENS
22.5 Integrative Mechanisms for Defecation
22.6 Epilogue
References
Chapter 23. Processing of Gastrointestinal Sensory Signals in the Brain
23.1 Introduction
23.2 Neuroanatomical Representation of GI Sensation
23.3 Functional Brain Imaging
23.4 Functional Brain Imaging of GI Sensation
23.5 Structural Brain Imaging
23.6 Summary
References
Chapter 24. Innervation of the Gastrointestinal Tract by Spinal and Vagal Afferent Nerves
24.1 Introduction
24.2 Anatomy of the Afferent Innervation
24.3 Structure–Function Relationships and Physiological Roles
24.4 Ion Channels and Receptors in Sensory Functions of Gastrointestinal Afferents
24.5 Changes in Gastrointestinal Afferents in Disease
24.6 Conclusion
References
Chapter 25. Neuroimaging of Brain–Gut Interactions in Functional Gastrointestinal Disorders
25.1 Introduction
25.2 The Current Role of Neuroimaging in FGIDS
25.3 Neuroimaging of Pain in FGIDS
25.4 Neuroimaging to Probe Specific Receptor Systems: PET
25.5 Emerging Neuroimaging Techniques
25.6 Multimodal Imaging
25.7 Moving Neuroimaging of the Brain–Gut Axis into the Future
References
Chapter 26. The Neurobiology of Gustation
26.1 Basic Anatomy of the Gustatory System
26.2 The Taste Bud: the Functional Unit of the Peripheral Gustatory System
26.3 Receptors and Peripheral Transduction Mechanisms
26.4 Fat Detection and Taste
26.5 Gustatory Signaling Cascades are Expressed in Other Chemosensory Systems
Acknowledgments
References
Chapter 27. Enteric Neural Regulation of Mucosal Secretion
27.1 Physiology of Water and Electrolyte Transport Across the Mucosa
27.2 Basic Mechanisms of Absorption and Secretion
27.3 Secretomotor Neurons
27.4 Secretomotor Pathways
27.5 Significant Mediators Other than VIP and ACh
27.6 Local Reflexes
27.7 Enteric Reflexes Running Via the Myenteric Plexus
27.8 Sensory Transduction
27.9 Coupling Motility and Secretion
27.10 Pathophysiology of Intestinal Secretion
References
Chapter 28. Hypothalamic-Pituitary-Adrenal Axis in Gastrointestinal Physiology
28.1 Introduction
28.2 Anatomy of the Human Hypothalamus
28.3 Integration of Autonomic and Endocrine Function by the Hypothalamus
28.4 CRH
28.5 Receptors of CRH
28.6 CRH-Binding Protein
28.7 ACTH
28.8 Glucocorticoid and Receptors of the Glucocorticoid
28.9 Stress-Induced Changes in Gastrointestinal Function and the Role of CRH
28.10 Animal Evidence of CRH on Gastrointestinal Motor Function
28.11 Animal Evidence of CRH on Visceral Sensation and Emotion
28.12 Clinical Evidence of CRH on Gastrointestinal Sensorimotor Function
28.13 Clinical Evidence of CRH Antagonist on Gastrointestinal Sensorimotor Function
28.14 Clinical Evidence of CRH Antagonist on Brain Function Under Colorectal Distension
28.15 Inflammation of the Gut and CRH
28.16 Differential Role of CRH-R1 and CRH-R2
28.17 Conclusion
Acknowledgment
References
Chapter 29. Neural Regulation of Gastrointestinal Blood Flow
29.1 Physiologic Relevance of Gastrointestinal Circulation
29.2 Anatomic and Functional Organization of GI Circulation
29.3 Innervation of GI Blood Vessels
29.4 Functional Implications of Vasomotor Neurons in the Regulation of GI Blood Flow
29.5 Interactive Control of GI Circulation
29.6 Physiologic and Pathologic Implications
29.7 Summary
Acknowledgments
References
Chapter 30. Neuromuscular Function in the Biliary Tract
30.1 The Gallbladder
30.2 The Sphincter of Oddi
References
Chapter 31. Brainstem Control of the Gastric Function
31.1 Efferent Autonomic Overlay
31.2 Visceral Afferent Inputs to Brainstem Reflex Control Circuits
31.3 Reflex Actions Triggered by Visceral Afferent Inputs
31.4 Components and Characteristics of Vagovagal Gastric Control Reflexes
31.5 Summary
References
Chapter 32. Physiology of Aerodigestive Reflexes in Neonates and Adults
32.1 Pharyngeal Motor Function: Anatomical Relationships
32.2 Pharyngeal Motor Function During Deglutition
32.3 Nasopharyngeal Motor Function During Swallowing and Belching
32.4 The Ues and Its Pressure Phenomena
32.5 Cerebral Cortical Representation of Pharyngeal/Reflexive and Volitional Swallow in Humans
32.6 Mechanisms of Airway Protection During Belching
References
Chapter 33. Motor Function of the Pharynx, the Esophagus, and Its Sphincters
33.1 Introduction
33.2 Central Pattern Generator and Brainstem
33.3 Pharynx — Anatomy, Neural Innervation, and Motor Pattern
33.4 UES
33.5 Neuromuscular Anatomy of the Esophagus and LES
33.6 Extrinsic Innervation: Parasympathetic and Sympathetic
33.7 Interstitial Cells of Cajal
33.8 Recording Techniques
33.9 Motor Patterns of the Esophagus — Aboral and Oral Transport
33.10 Deglutitive Inhibition and Muscle Refractoriness
33.11 Peristalsis in the Longitudinal Muscles of the Esophagus
33.12 Neural and Myogenic Mechanism of Peristalsis
33.13 Central Mechanism of Peristalsis — Cortical and Brainstem Control
33.14 Peripheral Mechanisms of Peristalsis
33.15 Central Versus Peripheral Mechanism of Deglutitive Inhibition
33.16 Neural Control of Longitudinal Muscle Contraction
33.17 Modulation of Primary and Secondary Peristalsis
33.18 Neural Control of the LES and Crural Diaphragm
33.19 The LES – Tonic Contraction
33.20 Swallow-Induced LES Relaxation
33.21 Crural Diaphragm Contribution to EGJ and Neural Control
33.22 Transient LES Relaxation and Pharmacological Inhibition
33.23 Compliance of the EGJ
References
Chapter 34. Neurophysiologic Mechanisms of Gastric Reservoir Function
34.1 Functional Anatomy
34.2 Different Phases of Gastric Motility
34.3 Measurement of Gastric Reservoir Function
34.4 Control of the Accommodation Reflex
34.5 Pathophysiologic Role of Impaired Accommodation
34.6 Conclusion
References
Chapter 35. Physiology of the Antral Pump and Gastric Emptying
35.1 Overview
35.2 Functional Anatomy
35.3 Innervation of the Distal Stomach
35.4 Tools to Study Gastric Emptying and Antropyloric Motility
35.5 Patterns of Antroduodenal Motor Activity
35.6 Integration of Motor Activity Involving the Antrum, Pylorus, and Duodenum
35.7 Conditions Associated with Disordered Gastric Emptying
35.8 Therapy for Delayed Gastric Emptying
References
Chapter 36. Neurophysiologic Mechanisms of Human Large Intestinal Motility
36.1 Introduction
36.2 Anatomy and Basic Control Mechanisms
36.3 Colonic Elecrophysiology
36.4 Innervation of the Colon
36.5 Measuring Colonic Perception and Motor Patterns
36.6 Colonic Motor Patterns
36.7 In vitro Studies of Colonic Motility
36.8 Modulators of Colonic Motility
36.9 Disorders of Colonic Motility
Acknowledgments
References
Chapter 37. Neuromuscular Physiology of the Pelvic Floor
37.1 Introduction
37.2 Anatomy
37.3 PFM Activity
37.4 Urethral and Anal Rhabdosphincters
37.5 PFMs and Pelvic Organ Function
37.6 PFMS and Neurologic Lesions
Acknowledgments
References
Section III Host Defense Mechanisms
Chapter 38. Tight Junctions and the Intestinal Barrier
38.1 Introduction
38.2 Intrinsic and Extrinsic Elements of the Barrier
38.3 The Intestinal Epithelial Barrier and Transcellular and Paracellular Transport
38.4 Protein Components of the TJ
38.5 Regulation of Intestinal Epithelial TJ Barrier
38.6 Clinical Disorders of Intestinal TJ Barrier Defect
38.7 Concluding Remarks
References
Chapter 39. Biology of Gut Immunoglobulins
39.1 Introduction
39.2 Origin of Gut Plasma Cells and Local Immunoglobulin Production
39.3 Polymeric Immunoglobulins and the Polymeric Immunoglobulin Receptor
39.4 IgG and the Neonatal Fc Receptor FcRn
39.5 IgE, FcεRI, and FcεRII
39.6 Conclusion
References
Chapter 40. Gastrointestinal Microbial Ecology with Perspectives on Health and Disease
40.1 Introduction
40.2 Overview of Culture-Independent Molecular Techniques for Characterizing the Human Gut Microbiome
40.3 Applying the Principles of Microbial Ecology to Analyze the Human Gut Microbiome
40.4 Membership and Diversity of the Human Gut Microbiome
40.5 Colonization and Succession of the Human Gut Microbiome
40.6 Modulation of the Gut Microbiota
40.7 Bacteria, their Metabolites, and Human Health
40.8 Perspectives on Health and Disease
References
Chapter 41. Mucosal Bacterial Recognition and Signaling Systems in the Intestine
41.1 Introduction
41.2 Functional Structure of PRRs
41.3 Expression of PRRs in the Gastrointestinal Tract
41.4 Bacterial Signaling Pathways and the Regulation of Mucosal Immunity
41.5 Physiological Roles of PRRS in the Gastrointestinal Mucosa
41.6 Concluding Remarks
References
Chapter 42. Mucosal Restitution and Repair
42.1 Introduction
42.2 Overview Of The Restitution Process
42.3 Modeling Restitution and Wound Healing
42.4 Regulation of Epithelial Wound Healing by Extracellular Signals
42.5 Intracellular Pathways Coordinating Migration
42.6 Relationship of Altered Migration to Disease
42.7 Future Challenges
References
Chapter 43. Gastroduodenal Mucosal Defense
43.1 Introduction
43.2 Animal Models of Gastroduodenal Injury
43.3 Juxtamucosal Environment and Pre-Epithelial Defenses
43.4 Gastroduodenal Epithelial Layer
43.5 Subepithelial Defense: Mucosal Blood Flow, Neurohormonal Effectors, Receptors, and Chemical Mediators
43.6 Injury and Restitution
43.7 Summary and Conclusions
Acknowledgments
References
VOLUME 2
Section IV Physiology of Secretion
Chapter 44. Paneth Cells
44.1 Introduction
44.2 Concluding Statement
References
Chapter 45. Salivary Gland Secretion
45.1 Introduction
45.2 Salivary Gland Development
45.3 Microscopic Anatomy
45.4 Secretion of Salivary Fluid and Electrolytes
45.5 Primary Saliva Secretion by Secretory Endpieces
45.6 Fluid Secretion Mechanism
45.7 Primary Saliva is Modified by the Salivary Gland Ducts
45.8 Protein Secretion
45.9 Factors Modulating Sorting of Secretory Proteins
45.10 Multiple Secretory Pathways in Salivary Gland Cells
45.11 Exocytosis
45.12 Functional Properties of Saliva
45.13 Saliva as a Diagnostic Fluid
References
Chapter 46. The Cell Biology of Gastric Acid Secretion
46.1 Cellular Plasticity of Gastric Acid Secretion
46.2 Molecular Mechanism of Hydrochloric Acid Secretion
46.3 Actin Cytoskeleton Plasticity in Parietal Cell Secretion
46.4 Stimulation-Secretion Coupling in the Parietal Cells
References
Chapter 47. Regulation of Gastric Acid Secretion
47.1 Introduction
47.2 Methods for Measurement of Gastric Acid Secretion
47.3 Functional Anatomy
47.4 Regulation of Gastric Acid Secretion: Central, Peripheral, and Intracellular Pathways
Acknowledgment
References
Chapter 48. Gastroduodenal Bicarbonate Secretion
48.1 Introduction
48.2 Gastric Secretion of HCO3−
48.3 Transport Proteins Involved in Gastric HCO3− Secretion
48.4 Regulation of Gastric HCO3− Secretion
48.5 Physiological Significance of Gastric HCO3− Secretion
48.6 Duodenal Secretion of HCO3−
48.7 Transport Proteins in Duodenal HCO3− Secretion
48.8 Physiological Regulation of Duodenal Bicarbonate Secretion
48.9 Summary and Future Directions
References
Chapter 49. Structure–function Relationships in the Pancreatic Acinar Cell
49.1 Organization of the Exocrine Pancreas
49.2 Pancreatic Development
49.3 Structural Organization
49.4 Functional Responses of the Acinar Cell: Protein Synthesis, Vectorial Transport, Modifications, and Sorting
49.5 Cell Signaling
49.6 Secretion
49.7 Early Acinar Cell Responses in Acute Pancreatitis
Acknowledgments
References
Chapter 50. Stimulus-secretion Coupling in Pancreatic Acinar Cells
50.1 Introduction
50.2 Receptors and Transmembrane Signaling
50.3 Intracellular Messengers
50.4 Action of Intracellular Messengers
50.5 Mechanisms of Exocytosis
References
Chapter 51. Cell Physiology of Pancreatic Ducts
51.1 Patterns Of Pancreatic Electrolyte Secretion
51.2 Structural Basis Of Secretion
51.3 Advances In Studying Duct Cell Physiology
51.4 Mechanisms Of Ductal Electrolyte Secretion
51.5 Regulation Of Ductal Bicarbonate Secretion
51.6 Concluding Remarks
References
Chapter 52. Regulation of Pancreatic Secretion
52.1 Patterns of Secretion
52.2 Phases of the Meal Response
52.3 Neural and Hormonal Regulators
52.4 Inhibition of Pancreatic Secretion
52.5 Pancreatic Function Testing
References
Chapter 53. Bile Formation and the Enterohepatic Circulation
53.1 Introduction to the Structure and Major Functions of Bile Acids
53.2 Biosynthesis, Chemistry, and Physical Chemistry of Bile Acids
53.3 Enterohepatic Circulation of Bile Acids
53.4 Bile Secretion and Hepatic Bile Acid Transport
53.5 Intestinal Absorption of Bile Acids
References
Chapter 54. Mechanisms of Hepatocyte Organic Anion Transport
54.1 Introduction
54.2 Mechanisms of Non-Bile Acid Organic Anion Uptake
54.3 Mechanisms of Bile Acid Uptake
54.4 Organic Anion Excretion Across the Bile Canaliculus
References
Chapter 55. Mechanisms of Hepatocyte Detoxification
55.1 Introduction
55.2 Metabolism and Excretion
55.3 Detoxification of Metals
55.4 Liver Self-Defense Mechanisms
55.5 Summary
References
Section V Digestion and Absorption
Chapter 56. Physiology of Cholangiocytes
56.1 Functional Anatomy of the Biliary Tract
56.2 Molecular Physiology of Ductal Bile Formation
56.3 Intracellular Signaling
56.4 Regulation of Ductal Bile Formation
56.5 Conclusion
References
Chapter 57. Molecular Mechanisms of Protein Sorting in Polarized Epithelial Cells
57.1 Introduction to Epithelial Cell Polarity
57.2 Cytoarchitecture and Membrane Compartments in Polarized Epithelial Cells
57.3 Sorting Pathways
57.4 Post-Endocytic Pathway
57.5 Sorting Signals
57.6 Recognition of Sorting Signals
57.7 Polarized Transport and Delivery
57.8 Polarized Docking and Fusion
57.9 Selective Retention
57.10 Summary
References
Chapter 58. Sugar Absorption
58.1 Overview
58.2 Absorption of Glucose, Galactose, and Fructose
58.3 The SGLT Gene Family
58.4 The GLUT Gene Family
58.5 SGLT1, GLUT2, and GLUT5 are the Major Intestinal Sugar Transporters
58.6 SGLT1 Sugar Selectivity
58.7 GLUT Sugar Selectivity
58.8 SGLT1 Cation Selectivity
58.9 Transport Kinetics
58.10 Genetic Defects
58.11 Regulation of Sugar Absorption
58.12 Future Directions
Acknowledgments
References
Chapter 59. Protein Digestion and Absorption
59.1 An Overview of Protein Digestion and Absorption
59.2 Role of Gastric and Pancreatic Proteases in Protein Digestion
59.3 Role of Membrane-Bound and Cytoplasmic Peptidases in the Enterocyte in Protein Digestion
59.4 Sites of Protein Absorption
59.5 Generation of Driving Forces for Active Transport Systems in the Enterocyte
59.6 Entry of Protein Digestion Products into the Enterocyte across the Brush Border Membrane
59.7 Fate of Absorbed Amino Acids and Peptides in the Enterocyte
59.8 Exit of Protein Digestion End Products across the Basolateral Membrane
59.9 Transport of Glutathione in the Small Intestine
59.10 Genetic Disorders of Intestinal Amino Acid and Peptide Transport
59.11 Nutritional, Clinical, and Pharmacological Relevance of Intestinal Peptide Transport
59.12 Regulation of Intestinal Amino Acid and Peptide Transport
59.13 Conclusions and Future Perspectives
References
Note Added in Proof
Chapter 60. Enterocyte Fatty Acid Handling Proteins and Chylomicron Formation
60.1 Overview of Dietary Fat Absorption
References
Chapter 61. Genetic Regulation of Intestinal Lipid Transport and Metabolism
61.1 Major Pathways and Genes Involved in Intestinal Triglyceride-Rich Lipoprotein Assembly
61.2 Genetic Defects in APOB and MTTP
61.3 Apolipoprotein B mRNA Editing: Overview, Molecular Mechanisms, and Functional Relevance
61.4 Other Genes Involved in Intestinal Lipoprotein Biogenesis: Apolipoprotein A-I and Apolipoprotein A-IV
61.5 Major Pathways and Genes Involved in Intestinal Sterol Transport
61.6 Other Genetic Defects of Intestinal Lipoprotein Assembly and Secretion and Potential New Pathways
References
Chapter 62. Digestion and Intestinal Absorption of Dietary Carotenoids and Vitamin A
62.1 Introduction
62.2 Carotenoid and Vitamin a Metabolism — Overview
62.3 Dietary Sources and Forms
62.4 Solubilization of Carotenoids and Retinoids
62.5 Conversion of Provitamin a Carotenoids to Retinoids
62.6 Digestion of Retinyl Esters
62.7 Intestinal Absorption of Carotenoids
62.8 Intestinal Absorption of Vitamin A
62.9 Overview
References
Chapter 63. 1,25-Dihydroxyvitamin D3
63.1 Introduction
63.2 Overview of Vitamin D Production and Physiology
63.3 The Molecular Mechanism of Action of 1,25(OH)2D3
63.4 New Insights into the Regulation of Gene Expression by 1,25(OH)2D3
63.5 The Transport of Calcium Across the Intestinal Epithelium
63.6 Regulation of Calcium Transporter Expression by 1,25(OH)2D3
63.7 Vitamin D Actions in the Colon: A New VDR Ligand, Xenobiotic Metabolism, and Anti-Carcinogenic and Anti-Cancer Actions
63.8 Vitamin D Therapeutics and the Calcemic Side Effects
63.9 Summary
References
Chapter 64. Mechanisms and Regulation of Intestinal Absorption of Water-soluble Vitamins
64.1 Vitamin B1 (Thiamin)
64.2 Vitamin B2 (Riboflavin)
64.3 Vitamin B3 (Niacin, Nicotinic Acid)
64.4 Vitamin B5 (Pantothenic Acid)
64.5 Vitamin B6 (Pyridoxine and Derivatives)
64.6 Vitamin B9 (Folate)
64.7 Vitamin B12 (Cobalamin)
64.8 Vitamin C (Ascorbic Acid)
64.9 Vitamin H (Biotin)
64.10 Concluding Remarks
References
Chapter 65. Water Transport in the Gastrointestinal Tract
65.1 Introduction
65.2 Epithelial Fluid Transporting Mechanisms
65.3 AQPs
65.4 Fluid Transport Mechanisms and AQPs in GI Organs
65.5 Summary and Perspective
References
Chapter 66. Na+/H+ Exchange in Mammalian Digestive Tract
66.1 Introduction
66.2 Mammalian Monovalent Cation Proton Antiporter Superfamily
66.3 Membrane Topology and Functional Domains
66.4 Transport Characteristics and Pharmacology
66.5 Gastrointestinal Na+/H+ Exchangers
66.6 Physiological Role of Na+/H+ Exchange in the Digestive Tract
Acknowledgments
References
Chapter 67. Intestinal Anion Absorption
67.1 Mechanisms of Intestinal Chloride Absorption
67.2 Mechanisms of SCFA Absorption
67.3 Mechanisms of Intestinal SO42− Absorption
67.4 Mechanisms of Intestinal Oxalate Absorption
67.5 Conclusions
Acknowledgments
References
Chapter 68. cAMP Sensor Epac and Gastrointestinal Function
68.1 Introduction
68.2 Identification of Epac as A Transducer of Intracellular cAMP Action
68.3 Epac Protects Hepatocytes from Apoptosis
68.4 Epac Participates in the Regulation of Intestinal Epithelial Cell Cl− Secretion
68.5 Conclusion
Acknowledgments
References
Note Added in Proof
Chapter 69. Ion Channels of the Epithelia of the Gastrointestinal Tract
69.1 CFTR in Chloride Transport in the Gastrointestinal Tract
69.2 Calcium-Activated Chloride Channels
69.3 CLC Family of Chloride Channels ClC-2
69.4 Summary
69.5 Epithelial Sodium Channel
69.6 Potassium Channels
69.7 Human Tissues and Human Cell Models: Species Differences
69.8 Methods for Study of Ion Channels in Gastrointestinal Tissues
69.9 Summary
References
Chapter 70. Molecular Mechanisms of Intestinal Transport of Calcium, Phosphate, and Magnesium
70.1 Introduction
70.2 Recommended Nutritional Requirements for Ca2+, Mg2+, and Pi
70.3 Intestinal Calcium Transport
70.4 Intestinal Phosphate Transport
70.5 Intestinal Transport of Magnesium
70.6 Conclusions
References
Chapter 71. Molecular Mechanisms of Intestinal Iron Transport
71.1 Introduction
71.2 The Anatomy of Iron Absorption — Specialization of the Proximal Small Intestine
71.3 Dietary Forms of Iron and Factors Affecting Luminal Bioavailability
71.4 Iron Transport Across the Enterocyte
71.5 Regulation of Iron Absorption
71.6 Developmental Changes in Iron Absorption
71.7 Pathological Conditions and Intestinal Iron Transport
71.8 Conclusions
References
Section VI Consequences of Disregulated Physiology
Chapter 72. Trace Element Absorption and Transport
72.1 General Properties of Trace Element Absorption
72.2 Other Trace Elements
Acknowledgment
References
Chapter 73. The Gastrointestinal Tract and Control of Food Intake
73.1 Signals Arising from the Gut in Control of Food Intake
73.2 Vagus Nerve
73.3 Processing of Information in the CNS
73.4 The Gut and Changes in Food Intake in Obesity
References
Chapter 74. Effects of Stress on Intestinal Mucosal Functions
74.1 Introduction
74.2 Mucosal Barrier Function
74.3 What is Stress?
74.4 Stress-induced Changes in Intestinal Mucosal Function
74.5 Consequences of Stress-Induced Changes in Mucosal Function in Relation to Human Intestinal Diseases
74.6 Conclusions
References
Chapter 75. Enteric Neurobiology of Stress
75.1 Stress: Case Examples
75.2 Stress and the Sympathetic Nervous System
75.3 Psychogenic Stress and Functional Gastrointestinal Disorders
75.4 Psychogenic Stress and Enteric Mast Cells
75.5 Neurobiology of Stress
75.6 CRF Receptors
75.7 Sources for CRF
References
Chapter 76. Mechanisms of Helicobacter pylori-induced Gastric Inflammation
76.1 Introduction
76.2 Colonization of the Gastric Mucosa
76.3 Evasion of the Host Immune Response by H. pylori
76.4 Development of Gastritis
76.5 H. pylori Strain Variation, Gastric Inflammation and Disease
76.6 Human Genetic Polymorphisms that Influence the Propensity Toward Development of Disease
76.7 Conclusions
References
Chapter 77. Physiology of Host-pathogen Interactions
77.1 Toxin-Mediated Effects on Ion Secretion
77.2 Absorption
77.3 Indirect Effects on Ion Secretion
77.4 Barrier Function and Cytotoxicity
77.5 Infection-Mediated Barrier Changes
77.6 Junctions as Pathogen Receptors
77.7 Pharmacopeia
77.8 Summary
References
Chapter 78. Mechanisms and Consequences of Intestinal Inflammation
78.1 Overview of Gut Function
78.2 Initiators and Mediators of Acute Intestinal Inflammation
78.3 Effectors of the Response to Luminal Triggers of Inflammation
78.4 Resolution Phase of Inflammation
78.5 Chronic Inflammation
78.6 Characterizing Inflammatory Disorders of the Intestine
78.7 Factors Contributing to the Development of Intestinal Inflammation
78.8 Summary
78.9 Effects of Inflammation on Intestinal Function
78.10 Summary
78.11 Future Directions for Research
References
Chapter 79. Recruitment of Inflammatory and Immune Cells in the Gut
79.1 Introduction
79.2 Adhesion Molecules
79.3 Regulation of Blood Cell–Endothelial Cell Interactions in Non-Lymphoid Tissues
79.4 Gut-Associated Lymphoid Tissue and Intestinal Immunity
79.5 Leukocyte Movement Through the Interstitium
79.6 Leukocyte Trafficking During Acute Inflammation
79.7 Leukocyte Trafficking During Chronic Gut Inflammation
Acknowledgments
References
Chapter 80. Mechanisms of GI Malignancies
80.1 Principles of Oncogenesis
80.2 Cardinal Features of Gastrointestinal Cancers
80.3 Genetic Instability
80.4 Novel Molecular Mechanisms Contributing to Gastrointestinal Carcinogenesis
80.5 Summary and Conclusions
References
Chapter 81. Pathophysiology Underlying the Irritable Bowel Syndrome
81.1 Irritable Bowel Syndrome
81.2 Neuropathy in the Brain-in-the-Gut
81.3 Neurogenic Secretion: Diarrhea and Constipation
81.4 Abdominal Pain and Discomfort
81.5 Psychogenic Stress
References
Chapter 82. Pathophysiology of Diarrhea and its Clinical Implications
82.1 Introduction
82.2 Physiology of Intestinal Absorption and Secretion
82.3 Definitions of Diarrhea
82.4 Pathophysiology of Diarrhea
82.5 Clinical Manifestations
82.6 Evaluation and Management
82.7 Conclusions
References
Index
HS
He serves as a reviewer on a variety of NIH, VA and other national study sections as well as international (European) study sections dealing with medical research in internal medicine and nutrition. He is also a member of Editorial Boards of a number of prestigious medical research journals.
Research in Dr. Said laboratory focuses on understanding cellular and molecular mechanisms involved in the transport of water-soluble vitamins (folate (vit. B), thiamine (vit. B1), riboflavin (vit. B2), pyridoxine (vit. B6), ascorbic acid (vit. C), biotin (vit. H) and niacin (vit. B3)) in the intestine, kidney, liver and pancreas. Dr. Said's laboratory has published over 160 original research papers in the gastrointestinal and nutrition fields. He has authored many chapters in scientific textbooks as well as a book in these areas. His laboratory has contributed many original discoveries to the field over the years. His research activities are funded by the VA and National Institutes of Health over the past twenty four years.