Physiology of the Gastrointestinal Tract

Physiology of the Gastrointestinal Tract

von: Kim E. Barrett, Fayez K. Ghishan, Juanita L. Merchant (Eds.)

Elsevier Trade Monographs, 2006

ISBN: 9780080456157 , 2080 Seiten

4. Auflage

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Physiology of the Gastrointestinal Tract


 

front cover

1

copyright

5

table of contents

6

front matter

12

body

24

Volume 1

1

Volume 1 Contents

6

Volume 1 Contributors

12

Volume 1 Preface to the First Edition

20

Volume 1 Preface

22

Volume 1 Acknowledgments

23

1 Transcriptional and Epigenetic Regulation

24

OVERVIEW OF GENE ORGANIZATION

24

EPIGENETIC INFLUENCES

28

ANATOMY OF THE PROMOTER

32

METHODOLOGY

39

TRANSCRIPTIONAL CONTROL OF GASTROINTESTINAL PEPTIDES

42

POSTTRANSCRIPTIONAL PROCESSING

42

TRANSPORT ACROSS THE NUCLEAR MEMBRANE

44

CONCLUSION

45

ACKNOWLEDGMENTS

45

REFERENCES

45

2 Translation and Posttranslational Processing of Gastrointestinal Peptides

54

TRANSLATION

54

POSTTRANSLATIONAL PROCESSING

58

TRANSPORT INTO THE ENDOPLASMIC RETICULUM

58

PROCESSING IN THE ENDOPLASMIC RETICULUM

61

TRANSPORT FROM THE ENDOPLASMIC RETICULUM AND THROUGH THE GOLGI

62

PROCESSING REACTIONS IN THE GOLGI

64

FORMATION OF SECRETORY VESICLES

65

PROCESSING REACTIONS IN THE SECRETORY VESICLE

65

POSTTRANSLATIONAL PROCESSING OF PREPROGASTRIN

71

REFERENCES

74

3 Transmembrane Signaling by G Protein-Coupled Receptors

86

STRUCTURE AND FUNCTION OF G PROTEIN-COUPLED RECEPTORS

87

MECHANISMS OF SIGNAL TRANSDUCTION

93

RECEPTOR TYROSINE KINASES ARE SIGNALING PARTNERS FOR G PROTEIN-COUPLED RECEPTORS

97

MECHANISMS THAT REGULATE SIGNALING BY G PROTEIN-COUPLED RECEPTORS

100

CONCLUSION

108

ACKNOWLEDGMENTS

108

REFERENCES

108

4 Gastrointestinal Hormones: Gastrin, Cholecystokinin, Somatostatin, and Ghrelin

114

GASTRIN

115

CHOLECYSTOKININ

123

SOMATOSTATIN

129

GHRELIN

132

REFERENCES

134

5 Postpyloric Gastrointestinal Peptides

144

SECRETIN

144

INTESTINAL SOMATOSTATIN

149

VASOACTIVE INTESTINAL POLYPEPTIDE AND RELATED PEPTIDES

149

NEUROTENSIN

153

NEUROPEPTIDE Y

157

MOTILIN

160

PEPTIDE YY

163

REFERENCES

171

6 Gastrointestinal Peptide Hormones Regulating Energy and Glucose Homeostasis

184

PROGLUCAGON GENE STRUCTURE AND THE PROGLUCAGON-DERIVED PEPTIDES

184

PROGLUCAGON-DERIVED PEPTIDE METABOLISM AND CLEARANCE

187

GLUCAGON RECEPTOR FAMILY

188

GLUCAGON RECEPTOR

188

GLUCAGON-LIKE PEPTIDE-1 RECEPTOR

188

GLUCAGON-LIKE PEPTIDE-2 RECEPTOR

189

GLUCOSE-DEPENDENT INSULINOTROPIC POLYPEPTIDE RECEPTOR

189

BIOLOGICAL ACTIONS OF GLUCAGON

189

GLUCAGON ADMINISTRATION IN HUMAN SUBJECTS

190

BIOLOGICAL ACTIONS OF GLICENTIN

190

OXYNTOMODULIN

190

BIOLOGICAL ACTIONS OF GLUCAGONLIKE PEPTIDE-1

190

GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONISTS AND THE TREATMENT OF TYPE 2 DIABETES

192

ENHANCING INCRETIN ACTION VIA INHIBITION OF DIPEPTIDYL PEPTIDASE-IV

193

BIOLOGICAL ACTIONS OF GLUCAGONLIKE PEPTIDE-2

193

GLUCAGON-LIKE PEPTIDE-2 ADMINISTRATION TO HUMAN SUBJECTS

194

GLUCOSE-DEPENDENT INSULINOTROPIC POLYPEPTIDE

194

REFERENCES

196

7 Growth Factors in the Gastrointestinal Tract

206

INTRODUCTION

207

TRANSFORMING GROWTH FACTOR-ß FAMILY OF PEPTIDES AND RECEPTORS

209

EPIDERMAL GROWTH FACTOR FAMILY OF PEPTIDES AND RECEPTORS

216

INSULIN-LIKE GROWTH FACTORS

228

TREFOIL FACTOR FAMILY OF PEPTIDES

232

HEPATOCYTE GROWTH FACTOR

236

FIBROBLAST GROWTH FACTOR FAMILY

239

REFERENCES

244

8 Developmental Signaling Networks

270

HISTORY

271

Wnt/ß-CATENIN PATHWAY

272

NONCANONICAL WNT SIGNALING PATHWAYS

283

WNT/ß-CATENIN PATHWAY IN GASTROINTESTINAL PHYSIOLOGY

283

WNT/ß-CATENIN PATHWAY DEFECTS IN GASTROINTESTINAL TUMORS

284

REFERENCES

287

9 Hedgehog Signaling in Gastrointestinal Morphogenesis and Morphostasis

294

PATTERNING

294

THE HEDGEHOG PATHWAY

295

ROLE OF HEDGEHOG SIGNALING IN THE DEVELOPMENT OF THE GUT

298

HEDGEHOG SIGNALING IN HOMEOSTASIS OF THE ADULT GASTROINTESTINAL TRACT

302

HEDGEHOG SIGNALING AND CARCINOGENESIS OF THE GASTROINTESTINAL TRACT

305

FUTURE DEVELOPMENTS

306

REFERENCES

306

10 Developmental Signaling Networks: The Notch Pathway

310

OVERVIEW OF NOTCH SIGNALING

310

STRUCTURE OF THE NOTCH RECEPTORS

311

STRUCTURE OF THE NOTCH LIGANDS

312

THE NOTCH SIGNALING PATHWAY

313

INTERACTIONS OF NOTCH WITH OTHER SIGNALING NETWORKS

317

NOTCH SIGNALING IN THE GASTROINTESTINAL SYSTEM

318

FUTURE DIRECTIONS

325

REFERENCES

325

11 Physiology of Gastrointestinal Stem Cells

330

WHAT IS A STEM CELL?

331

ORGANIZATION OF STRUCTURAL/PROLIFERATIVE UNITS IN THE GASTROINTESTINAL EPITHELIUM

331

MORPHOGENESIS OF THE GASTROINTESTINAL PROLIFERATIVE UNITS

332

CLONALITY OF THE STRUCTURAL/PROLIFERATIVE UNIT

333

STEM CELL NUMBER AND HIERARCHY

336

THE STEM CELL NICHE

338

REGULATION OF STEM CELL FUNCTION

339

STEM CELL PLASTICITY

358

CONCLUSION

359

ACKNOWLEDGMENTS

359

REFERENCES

359

12 Apoptosis in the Gastrointestinal Tract

368

CELL DEATH

368

INTESTINAL EPITHELIA: IN VIVO STUDIES

372

INTESTINAL CELLS: IN VITRO STUDIES

381

GASTRIC MUCOSA

387

CONCLUSION

389

REFERENCES

389

13 Molecular Aspects and Regulation of Gastrointestinal Function during Postnatal Development

398

ONTOGENY OF SECRETORY FUNCTION

399

ONTOGENY OF DIGESTIVE FUNCTION

400

ONTOGENY OF INTESTINAL TRANSPORT

402

ONTOGENY OF TRANSPORT FUNCTION ALONG THE VERTICAL AND HORIZONTAL GUT AXES

414

DEVELOPMENTAL REGULATION OF GASTROINTESTINAL FUNCTION

415

ACKNOWLEDGMENTS

417

REFERENCES

417

14 Effect of Aging on the Gastrointestinal Tract

428

THE AGING ESOPHAGUS

429

THE AGING STOMACH

430

THE AGING INTESTINE

434

AGING AND GASTROINTESTINAL CANCERS

437

REGULATION OF MUCOSAL GROWTH DURING AGING

443

AGING AND SURGERY OF THE GASTROINTESTINAL TRACT

446

ACKNOWLEDGMENTS

448

REFERENCES

448

15 Regulation of Gastrointestinal Normal Cell Growth

458

OVERVIEW

458

ORGANIZATION OF THE GASTROINTESTINAL MUCOSA

459

CELL CYCLE REGULATION

460

APOPTOSIS

460

SIGNAL TRANSDUCTION PATHWAYS REGULATING GASTROINTESTINAL DIFFERENTIATION AND GROWTH

463

GROWTH REGULATION BY LUMINAL NUTRIENTS AND SECRETIONS

472

GROWTH REGULATION BY SMALL PEPTIDE HORMONES AND THEIR RECEPTORS

474

FUTURE PERSPECTIVES/CLINICAL APPLICATIONS REFERENCES

476

16 Mucosal Repair and Restitution

482

OVERVIEW OF PROCESS

483

REGULATION OF EPITHELIAL WOUND HEALING BY EXTRACELLULAR SIGNALS

485

INTRACELLULAR PATHWAYS COORDINATING MIGRATION

488

METHODOLOGIES FOR STUDYING GASTROINTESTINAL CELL MIGRATION

490

RELATION OF ALTERED MIGRATION TO DISEASE

492

FUTURE CHALLENGES

493

REFERENCES

493

17 Mechanisms of Gastrointestinal Malignancies

500

PRINCIPLES OF ONCOGENESIS

500

CARDINAL FEATURES OF GASTROINTESTINAL CANCERS

504

GENETIC INSTABILITY

508

ACKNOWLEDGMENTS

515

REFERENCES

515

18 Development of the Enteric Nervous System

522

ORIGINS OF THE ENTERIC NERVOUS SYSTEM

524

CREST-DERIVED STEM CELLS ARE PRESENT IN THE DEVELOPING AND MATURE BOWEL

525

DEFECTS IN EARLY-ACTING FACTORS CAUSE EXTENSIVE AND VISIBLE ABNORMALITIES: HIRSCHSPRUNG'S DISEASE

526

DEFECTS IN LATE-ACTING FACTORS CAUSE RESTRICTED LESIONS OF THE ENTERIC NERVOUS SYSTEM

530

OTHER FACTORS IN ENTERIC NERVOUS SYSTEM DEVELOPMENT

534

ACKNOWLEDGMENTS

537

REFERENCES

537

19 Cellular Physiology of Gastrointestinal Smooth Muscle

546

SIGNAL TRANSDUCTION IN SMOOTH MUSCLE OF THE GUT

547

SIGNALING PATHWAYS FOR CONTRACTION

547

SIGNALING PATHWAYS FOR RELAXATION

550

CROSS-REGULATION: THE INTERPLAY OF SIGNALS IN A CHEMICAL PLAYGROUND

553

ACKNOWLEDGMENTS

554

REFERENCES

554

20 Organization and Electrophysiology of Interstitial Cells of Cajal and Smooth Muscle Cells in the Gastrointestinal Tract

556

ELECTRICAL ACTIVITY IN GASTROINTESTINAL MUSCLES

557

ROLE OF INTERSTITIAL CELLS OF CAJAL IN SPONTANEOUS ELECTRICAL RHYTHMICITY

558

ROLE OF INTERSTITIAL CELLS OF CAJAL IN NEUROTRANSMISSION

569

ROLE OF INTERSTITIAL CELLS OF CAJAL AS STRETCH RECEPTORS

571

MOTILITY DISORDERS ASSOCIATED WITH LOSS OF INTERSTITIAL CELLS OF CAJAL

572

ANIMAL MODELS TO STUDY LOSS OF INTERSTITIAL CELLS OF CAJAL

572

SMOOTH MUSCLE RESPONSES TO SLOW WAVES AND NEURAL INPUTS

573

INTEGRATION OF ELECTRICAL ACTIVITY IN GASTROINTESTINAL MUSCLES

592

ACKNOWLEDGMENTS

592

REFERENCES

592

21 Functional Histoanatomy of the Enteric Nervous System

600

OVERVIEW

600

INTRINSIC INNERVATION OF THE GUT WALL

605

EXTRINSIC INNERVATION OF THE GUT WALL

614

EXTRINSIC SENSORY NERVE ENDINGS

615

HEIRARCHIES OF NEUROCHEMICALS

617

SUMMARY AND CONCLUSIONS

618

ACKNOWLEDGMENTS

618

REFERENCES

618

22 Physiology of Prevertebral Sympathetic Ganglia

626

OVERVIEW

626

MORPHOLOGY

628

INNERVATION OF PREVERTEBRAL GANGLIA

630

CHEMICAL CODING OF PREVERTEBRAL GANGLION NEURONS

633

CHEMICAL CODING OF NERVE FIBERS IN PREVERTEBRAL GANGLIA

634

ORGANIZATION OF SYMPATHETIC MOTOR INNERVATION TO THE GUT

634

TARGETS IN THE GUT OF SYMPATHETIC NEURONS IN PREVERTEBRAL AND PELVIC GANGLIA

637

VISCERAL AFFERENT NEURONS

637

MORPHOLOGY OF VISCEROFUGAL NEURONS

639

CHEMICAL CODING OF VISCEROFUGAL NEURONS

642

POPULATIONS OF MECHANOSENSORY VISCEROFUGAL NEURONS ELECTROPHYSIOLOGY OF PREVERTEBRAL GANGLION NEURONS

643

PACEMAKER NEURONS

645

CONCLUDING REMARKS

646

ACKNOWLEDGMENTS

646

REFERENCES

647

23 Cellular Neurophysiology of Enteric Neurons

652

THE ENTERIC NERVOUS SYSTEM

652

AH- AND S-TYPE ENTERIC NEURONS

665

SYNAPTIC TRANSMISSION

669

REFERENCES

680

24 Integrative Functions of the Enteric Nervous System

688

INTEGRATED CONTROL OF THE STOMACH

689

INTEGRATED CONTROL OF THE SMALL AND LARGE INTESTINES

692

PLASTICITY IN THE ENTERIC NERVOUS SYSTEM

697

INTEGRATED CONTROL OF THE ANAL CANAL AND PELVIC FLOOR

701

INTEGRATIVE MECHANISMS FOR DEFECATION

704

EPILOGUE

705

REFERENCES

705

25 Extrinsic Sensory Afferent Nerves Innervating the Gastrointestinal Tract

708

DEVELOPMENTAL ASPECTS

708

ANATOMY OF EXTRINSIC AFFERENT FIBERS

710

NEUROPHYSIOLOGY OF EXTRINSIC GASTROINTESTINAL AFFERENTS

715

GASTROINTESTINAL EXTRINSIC AFFERENT NERVES: INTEGRATIVE PHYSIOLOGY

729

CONCLUSION

739

ACKNOWLEDGMENTS

739

REFERENCES

739

26 Processing of Gastrointestinal Sensory Signals in the Brain

750

NEUROANATOMIC REPRESENTATION OF GASTROINTESTINAL SENSATION

750

FUNCTIONAL BRAIN IMAGING

753

AN INTEGRATED VIEW OF GASTROINTESTINAL SENSORY PROCESSING IN THE BRAIN

757

REFERENCES

758

27 Enteric Neural Regulation of Mucosal Secretion

760

REFLEX MODULATION OF ENDOGENOUS "SECRETORY TONE"

761

FUNCTIONAL NEUROANATOMY OF SECRETORY REFLEXES

761

SENSORY ENTEROCHROMAFFIN/BON CELLS

764

SECRETORY REFLEXES

771

MEDIATORS OF SYNAPTIC TRANSMISSION IN SECRETORY REFLEXES

777

COORDINATION OF SECRETION AND MOTILITY

778

CYCLIC ADENOSINE MONOPHOSPHATE SIGNALING AND SECRETION

779

PATHOBIOLOGY OF REFLEX-DRIVEN INTESTINAL SECRETION

781

REFERENCES

784

28 Effect of Stress on Intestinal Mucosal Function

786

MUCOSAL BARRIER FUNCTION

786

STRESS CONCEPTS

789

STRESS-INDUCED CHANGES IN MUCOSAL FUNCTION IN HUMANS

790

STRESS-INDUCED CHANGES IN MUCOSAL FUNCTION IN ANIMALS

791

RELEVANCE FOR HUMAN INTESTINAL DISEASES

798

CONCLUSION

799

REFERENCES

799

29 Effect of Stress on Gastrointestinal Motility

804

EFFECTS OF STRESS ON GASTROINTESTINAL MOTILITY

805

CENTRAL CORTICOTROPIN-RELEASING FACTOR RECEPTORS AND STRESS- RELATED GASTROINTESTINAL MOTOR DISTURBANCES

806

AUTONOMIC DYSFUNCTION

807

PERIPHERAL CORTICOTROPIN-RELEASING FACTOR RECEPTORS INVOLVED IN STRESS-INDUCED COLONIC MOTOR ALTERATIONS

808

EFFECTS OF STRESS ON VISCERAL PERCEPTION

808

ROLE OF CORTICOTROPIN-RELEASING FACTOR RECEPTORS IN STRESS-INDUCED VISCERAL HYPERALGESIA

809

SEX DIFFERENCE IN STRESS-INDUCED VISCERAL HYPERSENSITIVITY

809

CONCLUSION

809

REFERENCES

810

30 Central Corticotropin-Releasing Factor and the Hypothalamic-Pituitary-Adrenal Axis in Gastrointestinal Physiology

814

HISTORICAL CONSIDERATIONS

814

CHEMISTRY OF THE HYPOTHALAMICPITUITARY-ADRENAL AXIS

815

BRAIN DISTRIBUTION OF CORTICOTROPIN-RELEASING FACTOR LIGANDS AND RECEPTORS

818

CENTRAL ACTION OF CORTICOTROPIN-RELEASING FACTOR PEPTIDES TO INFLUENCE GASTRIC FUNCTION

820

CENTRAL ACTIONS OF CORTICOTROPIN-RELEASING FACTOR PEPTIDES TO INFLUENCE SMALL INTESTINAL FUNCTION

825

CENTRAL ACTIONS OF CORTICOTROPIN-RELEASING FACTOR PEPTIDES TO INFLUENCE COLONIC FUNCTION

827

CONCLUSION

832

ACKNOWLEDGMENTS

832

REFERENCES

832

31 Neural Regulation of Gastrointestinal Blood Flow

840

PHYSIOLOGIC RELEVANCE OF THE GASTROINTESTINAL CIRCULATION

840

ORGANIZATIONAL CHARACTERISTICS OF THE GASTROINTESTINAL CIRCULATION

840

INNERVATION OF GASTROINTESTINAL BLOOD VESSELS

842

FUNCTIONAL IMPLICATIONS OF VASOMOTOR NEURONS IN THE REGULATION OF GASTROINTESTINAL BLOOD FLOW

843

INTERACTIVE CONTROL OF GASTROINTESTINAL CIRCULATION

853

SUMMARY

855

ACKNOWLEDGMENTS

855

REFERENCES

855

32 Neural Control of the Gallbladder and Sphincter of Oddi

864

GALLBLADDER

864

SPHINCTER OF ODDI

868

REFERENCES

870

33 Brainstem Control of Gastric Function

874

EFFERENT AUTONOMIC OVERLAY

875

VISCERAL AFFERENT INPUTS TO BRAINSTEM REFLEX CONTROL CIRCUITS

877

REFLEX ACTIONS TRIGGERED BY VISCERAL AFFERENT INPUTS

878

COMPONENTS AND CHARACTERISTICS OF VAGO-VAGAL GASTRIC CONTROL REFLEXES

879

SUMMARY

892

ACKNOWLEDGMENTS

892

REFERENCES

892

34 Neural and Hormonal Controls of Food Intake and Satiety

900

FOOD INTAKE AND ENERGY BALANCE METABOLIC SIGNALS AND THEIR MEDIATION

900

WITHIN-MEAL FEEDBACK SIGNALING

904

INTERACTIONS BETWEEN GUT PEPTIDE AND HYPOTHALAMIC SIGNALING

910

SUMMARY

911

REFERENCES

911

35 Pharyngeal Motor Function

918

PHARYNGEAL MOTOR FUNCTION DURING DEGLUTITION

918

PRESSURE PROFILE OF THE PHARYNX

919

PHARYNGEAL PRESSURE PHENOMENON IN RELATION TO SWALLOWED MATERIAL

921

DEGLUTITIVE LARYNGEAL MOTOR FUNCTION

923

UPPER ESOPHAGEAL SPHINCTER AND ITS PRESSURE PHENOMENA

925

OPENING OF THE UPPER ESOPHAGEAL SPHINCTER

926

UPPER ESOPHAGEAL SPHINCTER, PHARYNGOLARYNGEAL, AND ESOPHAGEAL REFLEXES

927

ESOPHAGOGLOTTAL CLOSURE REFLEX

927

PHARYNGEAL (SECONDARY) SWALLOW

928

CEREBRAL CORTICAL REPRESENTATION OF PHARYNGEAL/REFLEXIVE AND VOLITIONAL SWALLOW IN HUMANS

929

PHARYNGO-UPPER ESOPHAGEAL SPHINCTER CONTRACTILE REFLEX

930

PHARYNGOGLOTTAL ADDUCTION REFLEX

931

LARYNGO-UPPER ESOPHAGEAL SPHINCTER CONTRACTILE REFLEX

931

PHARYNGEAL INHIBITORY REFLEXES

931

MECHANISMS OF AIRWAY PROTECTION DURING BELCHING

932

REFERENCES

933

36 Motor Function of the Esophagus

936

OVERVIEW

936

NEUROMUSCULAR ANATOMY

936

INNERVATION

937

COORDINATED MOTOR EVENTS

939

REFERENCES

946

37 Neurophysiologic Mechanisms of Gastric Reservoir Function

950

FUNCTIONAL ANATOMY

950

DIFFERENT PHASES OF GASTRIC MOTILITY

950

MEASUREMENT OF GASTRIC RESERVOIR FUNCTION

951

CONTROL OF THE ACCOMMODATION REFLEX

952

PATHOPHYSIOLOGIC ROLE OF IMPAIRED ACCOMMODATION

954

CONCLUSION

954

REFERENCES

955

38 Small Intestinal Motility

958

ANATOMIC AND FUNCTIONAL CONSIDERATIONS

958

SMALL INTESTINAL TRANSIT

959

SPECIALIZED SMALL INTESTINAL CELL TYPES

959

COUPLING OF SMALL INTESTINAL CONTRACTIONS

963

CONTROL OF SMALL INTESTINAL PERISTALSIS

964

STEREOTYPICAL SMALL INTESTINAL MOTOR PATTERNS

966

EXTENDED REFLEXES INVOLVING THE SMALL INTESTINE

974

EXTERNAL INFLUENCES ON SMALL INTESTINAL MOTOR ACTIVITY

976

REFERENCES

979

39 Function and Regulation of Colonic Contractions in Health and Disease

988

FUNCTION AND SPATIOTEMPORAL CHARACTERISTICS OF COLONIC CONTRACTIONS

989

CELLULAR AND MOLECULAR REGULATION OF COLONIC CONTRACTIONS

992

COLONIC MOTOR DYSFUNCTION

1005

ACKNOWLEDGMENT

1010

REFERENCES

1010

40 Neural Control of Pelvic Floor Muscles

1018

INNERVATION OF PELVIC FLOOR MUSCLES

1018

PELVIC FLOOR MUSCLE ACTIVITY

1022

PELVIC FLOOR MUSCLES AND PELVIC ORGAN FUNCTION

1026

PELVIC FLOOR MUSCLES AND NEUROLOGIC LESIONS

1028

REFERENCES

1029

41 Pathophysiology Underlying the Irritable Bowel Syndrome

1032

NEUROPATHY IN THE BRAIN-IN-THE-GUT

1032

NEUROGENIC SECRETION: DIARRHEA AND CONSTIPATION

1036

ABDOMINAL PAIN AND DISCOMFORT

1038

PSYCHOLOGICAL STRESS

1045

REFERENCES

1050

Volume 1 Index

1056

Volume 2

1082

Volume 2 Contents

1087

Volume 2 Contributors

1093

Volume 2 Preface to the First Edition

1101

Volume 2 Preface

1103

Volume 2 Acknowledgments

1104

42 Innate Immunity

1105

SENSOR MOLECULES

1106

EFFECTOR MOLECULES

1121

REFERENCES

1129

43 Biology of Gut Immunoglobulins

1139

SECRETORY IMMUNOGLOBULIN A AND THE POLYMERIC IMMUNOGLOBULIN RECEPTOR

1140

IMMUNOGLOBULIN G AND THE NEONATAL Fc RECEPTOR FcRn

1149

IMMUNOGLOBULIN E

1154

CONCLUDING REMARKS

1157

REFERENCES

1157

44 Mechanisms of Helicobacter pylori-Induced Gastric Inflammation

1163

COLONIZATION OF THE GASTRIC MUCOSA

1164

EVASION OF THE HOST IMMUNE RESPONSE BY HELICOBACTER PYLORI

1166

DEVELOPMENT OF GASTRITIS

1167

HELICOBACTER PYLORI STRAIN VARIATION, GASTRIC INFLAMMATION, AND DISEASE

1171

HUMAN GENETIC POLYMORPHISMS THAT INFLUENCE THE PROPENSITY TOWARD DEVELOPMENT OF DISEASE

1176

CONCLUSION

1178

REFERENCES

1178

45 Mechanisms and Consequences of Intestinal Inflammation

1187

INTESTINAL INFLAMMATION

1187

EFFECTS OF INFLAMMATION ON INTESTINAL FUNCTION

1196

SUMMARY

1202

REFERENCES

1202

46 Recruitment of Inflammatory and Immune Cells in the Gut: Physiology and Pathophysiology

1209

ADHESION MOLECULES

1210

REGULATION OF BLOOD CELL-ENDOTHELIAL CELL INTERACTIONS IN NONLYMPHOID TISSUES

1215

GUT-ASSOCIATED LYMPHOID TISSUE AND INTESTINAL IMMUNITY

1220

LYMPHOCYTE HOMING AND ACTIVATION IN GUT-ASSOCIATED LYMPHOID TISSUE

1221

LEUKOCYTE MOVEMENT THROUGH THE INTERSTITIUM

1223

LEUKOCYTE TRAFFICKING DURING ACUTE INFLAMMATION

1225

LEUKOCYTE TRAFFICKING DURING CHRONIC GUT INFLAMMATION

1227

REFERENCES

1229

47 Physiology of Host-Pathogen Interactions

1235

TOXIN-MEDIATED EFFECTS ON ION SECRETION

1237

ABSORPTION: ENTEROPATHOGENIC

1243

INDIRECT EFFECTS ON ION SECRETION

1244

CYCLOOXYGENASE-2/NITRIC OXIDE/PROSTAGLANDIN E-MEDIATED Cl- SECRETION

1244

BARRIER FUNCTION AND CYTOTOXICITY

1245

INFECTION-MEDIATED BARRIER CHANGES

1250

SUMMARY

1254

REFERENCES

1254

48 The Cell Biology of Gastric Acid Secretion

1261

MORPHOLOGIC BASIS OF HYDROCHLORIC ACID SECRETION

1261

CELLULAR BASIS OF HYDROCHLORIC ACID SECRETION

1266

TRANSPORT AT THE BASOLATERAL MEMBRANE

1275

GETTING THE MESSAGE TO THE PARIETAL CELL

1277

SUPPORTING MEMBRANE TRANSFORMATIONS: THE VESICULAR TRAFFICKING MACHINERY

1281

REFERENCES

1288

49 Regulation of Gastric Acid Secretion

1295

FUNCTIONAL ANATOMY

1295

REGULATION OF GASTRIC ACID SECRETION

1297

DISORDERS OF GASTRIC ACID SECRETION

1318

REFERENCES

1319

50 Gastroduodenal Mucosal Defense

1331

JUXTAMUCOSAL ENVIRONMENT AND PREEPITHELIAL DEFENSES

1332

GASTRODUODENAL EPITHELIAL LAYER

1336

SUBEPITHELIAL DEFENSE: GASTRODUODENAL MUCOSAL BLOOD FLOW, NEURAL SENSORS AND EFFECTORS, AND CHEMICAL MEDIATORS

1345

INJURY AND RESTITUTION

1351

ANIMAL MODELS OF GASTRODUODENAL INJURY

1353

SUMMARY AND CONCLUSIONS

1354

ACKNOWLEDGMENTS

1354

REFERENCES

1354

51 Genetically Engineered Mouse Models of Gastric Physiology

1365

GENETIC ENGINEERING IN THE MOUSE

1365

OVERVIEW OF GASTRIC ACID SECRETION

1368

MICE WITH ACID REGULATORY MUTATIONS

1370

PARIETAL CELL CHANNEL AND TRANSPORTER MUTANTS

1376

OTHER GASTRIC MUTANTS

1378

TRANSGENE EXPRESSION IN THE GASTRIC MUCOSA

1378

CONCLUSION

1380

REFERENCES

1381

52 Structure-Function Relations in the Pancreatic Acinar Cell

1385

ORGANIZATION OF THE EXOCRINE PANCREAS

1385

PANCREATIC DEVELOPMENT

1386

STRUCTURAL ORGANIZATION

1388

FUNCTIONAL RESPONSES OF THE ACINAR CELL: PROTEIN SYNTHESIS, VECTORIAL TRANSPORT, MODIFICATIONS, AND SORTING

1391

CELL SIGNALING

1398

SECRETION

1402

ACKNOWLEDGMENTS

1406

REFERENCES

1406

53 Stimulus-Secretion Coupling in Pancreatic Acinar Cells

1409

RECEPTORS

1410

TRANSMEMBRANE SIGNALING

1410

INTRACELLULAR MESSENGERS

1411

INTRACELLULAR MESSENGER-INDUCED SECRETION

1425

ACTION OF INTRACELLULAR MESSENGERS

1426

MECHANISMS OF EXOCYTOSIS

1430

REFERENCES

1434

54 Cell Physiology of Pancreatic Ducts

1443

PATTERNS OF PANCREATIC ELECTROLYTE SECRETION

1443

STRUCTURAL BASIS OF SECRETION

1444

ADVANCES IN STUDYING DUCT CELL PHYSIOLOGY

1447

MECHANISMS OF DUCTAL ELECTROLYTE SECRETION

1450

REGULATION OF DUCTAL SECRETION

1457

CONCLUDING REMARKS

1463

REFERENCES

1463

55 Regulation of Pancreatic Secretion

1469

PATTERNS OF SECRETION

1469

PHASES OF THE MEAL RESPONSE

1472

NEURAL AND HORMONAL REGULATORS

1476

INHIBITION OF PANCREATIC SECRETION

1492

PANCREATIC FUNCTION TESTING

1495

REFERENCES

1496

56 Bile Formation and the Enterohepatic Circulation

1509

BIOSYNTHESIS, CHEMISTRY, AND PHYSICAL CHEMISTRY OF BILE ACIDS

1510

ENTEROHEPATIC CIRCULATION

1516

BILE SECRETION AND HEPATIC BILE ACID TRANSPORT

1518

CONCENTRATION OF BILE IN THE GALLBLADDER

1522

OVERVIEW OF INTESTINAL ABSORPTION OF BILE ACIDS

1523

FUNCTIONS AND DYSFUNCTIONS OF BILE ACIDS IN THE INTESTINE

1526

THERAPEUTIC USES OF BILE ACID AGONISTS AND ANTAGONISTS IN CLINICAL MEDICINE

1527

REFERENCES

1528

57 Mechanisms of Hepatocyte Organic Anion Transport

1535

MECHANISMS OF NONBILE ACID ORGANIC ANION UPTAKE

1535

MECHANISMS OF BILE ACID UPTAKE

1540

ORGANIC ANION EXCRETION ACROSS THE BILE CANALICULUS

1543

SUMMARY

1547

REFERENCES

1547

58 Mechanisms of Hepatocyte Detoxification

1555

OVERVIEW

1555

METABOLISM AND EXCRETION

1556

PROTECTION FROM DAMAGE

1564

SUMMARY

1573

ACKNOWLEDGMENTS

1573

REFERENCES

1573

59 Physiology of Cholangiocytes

1577

ARCHITECTURE AND PHENOTYPIC CHARACTERISTICS OF THE INTRAHEPATIC BILIARY DUCTAL SYSTEM (BRIEF OVERVIEW)

1578

MOLECULAR PHYSIOLOGY OF DUCTAL BILE FORMATION

1580

INTRACELLULAR SIGNALING

1585

REGULATION OF DUCTAL BILE FORMATION

1587

INTEGRATED MODEL OF DUCTAL BILE FORMATION

1596

CONCLUDING REMARKS

1597

ACKNOWLEDGMENTS

1597

REFERENCES

1597

60 Gallbladder Function

1607

GALLBLADDER MORPHOLOGY

1608

TECHNIQUES TO STUDY GALLBLADDER FUNCTION

1608

ELECTROLYTE AND WATER TRANSPORT

1609

BILIARY CHOLESTEROL ABSORPTION

1616

BILIRUBIN AND XENOBIOTIC TRANSPORT

1620

BILE SALT TRANSPORT

1621

TRANSPORT OF AMINO ACIDS AND SUGARS

1621

MUCINS

1621

PROTEIN ABSORPTION AND SECRETION

1623

BACTERIAL INFECTION, INFLAMMATION, AND GALLBLADDER FUNCTION

1623

SUMMARY

1625

REFERENCES

1625

61 Tight Junctions and the Intestinal Barrier

1631

INTRINSIC AND EXTRINSIC ELEMENTS OF THE BARRIER

1632

INTESTINAL EPITHELIAL BARRIER AND TRANSCELLULAR AND PARACELLULAR TRANSPORT

1632

PROTEIN COMPONENTS OF THE TIGHT JUNCTION

1637

REGULATION OF INTESTINAL EPITHELIAL TIGHT JUNCTION BARRIER

1640

CLINICAL DISORDERS OF INTESTINAL TIGHT JUNCTION BARRIER DEFECT

1654

REFERENCES

1658

62 Protein Sorting in the Exocytic and Endocytic Pathways in Polarized Epithelial Cells

1667

CYTOARCHITECTURE OF THE POLARIZED EPITHELIAL CELL

1667

CELL BIOLOGY TOOLKIT

1672

MOLECULAR MECHANISMS OF POLARIZED TRAFFIC

1672

CONCLUSION

1690

REFERENCES

1691

63 Physiology of the Circulation of the Small Intestine

1699

INTESTINAL MICROVASCULAR ANATOMY

1699

FACTORS THAT GENERATE VASOCONSTRICTION

1702

FACTORS THAT GENERATE VASODILATION

1706

POSTPRANDIAL HYPEREMIA

1712

ACKNOWLEDGMENTS

1719

REFERENCES

1719

64 Sugar Absorption

1725

OVERVIEW

1726

SGLT GENE FAMILY

1726

GLUT GENE FAMILY

1726

ABSORPTION OF GLUCOSE, GALACTOSE, AND FRUCTOSE

1726

SGLT1, GLUT2, AND GLUT5 ARE THE MAJOR INTESTINAL SUGAR TRANSPORTERS

1728

SGLT1 SUGAR SELECTIVITY

1728

GLUT SUGAR SELECTIVITY

1729

SGLT1 CATION SELECTIVITY

1729

TRANSPORT KINETICS

1730

GENETIC DEFECTS OF SUGAR ABSORPTION

1734

REGULATION OF SUGAR ABSORPTION

1735

FUTURE DIRECTIONS

1735

ACKNOWLEDGMENTS

1735

REFERENCES

1736

65 Protein Digestion and Absorption

1739

OVERVIEW

1740

ROLE OF GASTRIC AND PANCREATIC PROTEASES IN PROTEIN DIGESTION

1740

ROLE OF MEMBRANE-BOUND AND CYTOPLASMIC PEPTIDASES IN THE ENTEROCYTE IN PROTEIN DIGESTION

1741

SITES OF PROTEIN ABSORPTION

1741

GENERATION OF DRIVING FORCES FOR ACTIVE TRANSPORT SYSTEMS IN THE ENTEROCYTE

1742

ENTRY OF PROTEIN DIGESTION PRODUCTS INTO THE ENTEROCYTE ACROSS THE BRUSH-BORDER MEMBRANE

1743

FATE OF ABSORBED AMINO ACIDS AND PEPTIDES IN THE ENTEROCYTE

1749

EXIT OF PROTEIN DIGESTION END PRODUCTS ACROSS THE BASOLATERAL MEMBRANE

1749

TRANSPORT OF GLUTATHIONE IN THE SMALL INTESTINE

1753

GENETIC DISORDERS OF INTESTINAL AMINO ACID AND PEPTIDE TRANSPORT

1753

NUTRITIONAL, CLINICAL, AND PHARMACOLOGIC RELEVANCE OF INTESTINAL PEPTIDE TRANSPORT

1755

REGULATION OF INTESTINAL AMINO ACID AND PEPTIDE TRANSPORT

1756

CONCLUSIONS AND FUTURE PERSPECTIVES

1758

REFERENCES

1759

66 Role of Membrane and Cytosolic Fatty Acid Binding Proteins in Lipid Processing by the Small Intestine

1765

CELLULAR FATTY ACID UPTAKE

1765

FATTY ACID DELIVERY TO CELLS

1766

FACILITATED MEMBRANE TRANSFER OF FATTY ACIDS

1766

FATTY ACID UPTAKE BY ENTEROCYTES

1767

PROTEINS IMPLICATED IN FATTY ACID TRANSPORT THAT ARE EXPRESSED IN ENTEROCYTES

1768

INTRACELLULAR FATTY ACID TRANSPORT

1771

FATTY ACID-BINDING PROTEINS

1772

FUTURE DIRECTIONS

1776

REFERENCES

1776

67 Genetic Regulation of Intestinal Lipid Transport and Metabolism

1783

OVERVIEW

1783

MAJOR PATHWAYS AND GENES INVOLVED IN INTESTINAL TRIGLYCERIDE-RICH LIPOPROTEIN ASSEMBLY

1784

GENETIC DEFECTS IN APOB AND MTTP

1789

APOLIPOPROTEIN B MESSENGER RNA EDITING: OVERVIEW, MOLECULAR MECHANISMS, AND FUNCTIONAL RELEVANCE

1793

OTHER GENES INVOLVED IN INTESTINAL LIPOPROTEIN BIOGENESIS: APOLIPOPROTEINS A-I AND A-IV

1795

MAJOR PATHWAYS AND GENES INVOLVED IN INTESTINAL STEROL TRANSPORT

1796

OTHER GENETIC DEFECTS OF INTESTINAL LIPOPROTEIN ASSEMBLY AND SECRETION AND POTENTIAL NEW PATHWAYS

1800

ACKNOWLEDGMENTS

1801

REFERENCES

1801

68 Digestion and Intestinal Absorption of Dietary Carotenoids and Vitamin A

1807

CAROTENOID AND VITAMIN A METABOLISM: OVERVIEW

1807

DIETARY SOURCES AND FORMS

1809

SOLUBILIZATION OF CAROTENOIDS AND RETINOIDS

1810

CONVERSION OF PROVITAMIN A CAROTENOIDS TO RETINOIDS

1811

DIGESTION OF RETINYL ESTERS

1812

INTESTINAL ABSORPTION OF CAROTENOIDS

1813

INTESTINAL ABSORPTION OF VITAMIN A

1816

SUMMARY

1819

REFERENCES

1820

69 Vitamin D3: Synthesis, Actions, and Mechanisms in the Intestine and Colon

1825

OVERVIEW OF VITAMIN D PRODUCTION AND PHYSIOLOGY

1826

MOLECULAR MECHANISM OF ACTION OF 1,25-DIHYDROXYVITAMIN D

1828

TRANSPORT OF CALCIUM ACROSS THE INTESTINAL EPITHELIUM

1833

REGULATION OF CALCIUM TRANSPORTER EXPRESSION BY 1,25-DIHYDROXYVITAMIN D

1835

VITAMIN D THERAPEUTICS AND THE CALCEMIC SIDE EFFECTS

1837

VITAMIN D ACTIONS IN THE COLON: ANTICARCINOGENIC ACTIONS AND A NEW VITAMIN D RECEPTOR LIGAND

1837

SUMMARY

1838

REFERENCES

1839

70 Vitamin E and Vitamin K Metabolism

1845

VITAMIN E

1845

VITAMIN K

1853

ACKNOWLEDGMENTS

1857

REFERENCES

1857

71 Intestinal Absorption of Water-Soluble Vitamins

1863

FOLATE

1864

THIAMIN (VITAMIN B1)

1869

BIOTIN (VITAMIN H)

1874

VITAMIN C (ASCORBIC AND DEHYDROASCORBIC ACIDS)

1879

VITAMIN B6

1881

RIBOFLAVIN (VITAMIN B2)

1883

NIACIN (NICOTINIC ACID; VITAMIN B3)

1884

PANTOTHENIC ACID

1884

COBALAMIN (VITAMIN B12)

1885

ACKNOWLEDGMENTS

1891

REFERENCES

1891

72 Water Transport in the Gastrointestinal Tract

1899

EPITHELIAL FLUID-TRANSPORTING MECHANISMS

1900

AQUAPORINS

1904

FLUID TRANSPORT MECHANISMS AND AQUAPORINS IN GASTROINTESTINAL ORGANS

1907

SUMMARY AND PERSPECTIVE REFERENCES

1913

73 Na+-H+ Exchange in Mammalian Digestive Tract

1919

OVERVIEW

1919

MAMMALIAN NA+-H+ EXCHANGER GENE FAMILY

1920

GASTROINTESTINAL NA+-H+ EXCHANGERS

1927

PHYSIOLOGIC ROLES OF NA+-H+ EXCHANGE IN THE DIGESTIVE TRACT

1938

ACKNOWLEDGMENTS

1945

REFERENCES

1945

74 Intestinal Anion Absorption

1953

MECHANISMS OF INTESTINAL SULFATE ABSORPTION

1953

MECHANISMS OF INTESTINAL Cl- ABSORPTION

1954

MECHANISMS OF SHORT-CHAIN FATTY ACID ABSORPTION

1973

CONCLUSION

1979

ACKNOWLEDGMENTS

1980

REFERENCES

1980

75 Ion Channels of the Epithelia of the Gastrointestinal Tract

1989

CYSTIC FIBROSIS TRANSMEMBRANE REGULATOR IN CHLORIDE TRANSPORT IN THE GASTROINTESTINAL TRACT

1990

CALCIUM-ACTIVATED CHLORIDE CHANNELS

1991

CIC FAMILY OF CHLORIDE CHANNELS

1991

SUMMARY

1992

EPITHELIAL SODIUM CHANNEL

1992

POTASSIUM CHANNELS

1992

HUMAN TISSUES AND HUMAN CELL MODELS: SPECIES DIFFERENCES

1994

METHODS FOR STUDY OF ION CHANNELS IN GASTROINTESTINAL TISSUES

1994

SUMMARY

1997

REFERENCES

1997

76 Integrative Physiology and Pathophysiology of Intestinal Electrolyte Transport

2003

REGULATION OF INTESTINAL ION TRANSPORT AT THE CELLULAR LEVEL

2004

REGULATION OF INTESTINAL ION TRANSPORT AT THE TISSUE LEVEL

2011

ADAPTIVE AND MALADAPTIVE ALTERATIONS OF ION TRANSPORT IN DISEASE

2014

SUMMARY AND CONCLUSIONS

2016

ACKNOWLEDGMENTS

2017

REFERENCES

2018

77 Molecular Mechanisms of Intestinal Transport of Calcium, Phosphate, and Magnesium

2025

RECOMMENDED NUTRITIONAL REQUIREMENTS FOR Ca2+, Mg2+, AND INORGANIC PHOSPHATE

2025

INTESTINAL CALCIUM TRANSPORT

2026

INTESTINAL TRANSPORT OF PHOSPHATE

2039

INTESTINAL TRANSPORT OF MAGNESIUM

2043

ACKNOWLEDGMENTS

2047

REFERENCES

2047

78 Iron Absorption

2055

INTESTINAL IRON ABSORPTION

2055

PLASMA IRON TRAFFICKING

2057

SYSTEMIC IRON HOMEOSTASIS

2057

DISORDERS ASSOCIATED WITH ABNORMAL IRON ABSORPTION

2058

REFERENCES

2062

79 Trace Element Absorption and Transport

2065

GENERAL PROPERTIES OF TRACE ELEMENT ABSORPTION LUMENAL ENVIRONMENT AND TRACE ELEMENT ABSORPTION

2065

COPPER ABSORPTION

2067

ZINC ABSORPTION

2068

OTHER TRACE ELEMENTS

2070

REFERENCES

2070

Volume 2 Index

2073

Index

2073

Color Plates 1

1074

Color Plates 2

2091