Front Cover -- Physiology of the Gastrointestinal Tract -- Copyright Page -- Contents -- Contributors -- Preface to the First Edition -- Preface -- Acknowledgments -- Volume I -- Section I: Basic Cell Physiology, Genetics, and Growth of the GI Tract -- 1. Transcription and Epigenetic Regulation -- 1.1 Overview of Gene Organization -- 1.1.1 Nucleic Acids -- 1.1.2 Nucleic Acid Polymers: DNA, RNA -- 1.1.3 Gene Composition -- 1.1.4 RNA Species -- 1.1.5 Linking Gene Structure to Function -- 1.2 Epigenetic Influences -- 1.2.1 DNA Methylation -- 1.2.2 Histone Modifications -- 1.2.2.1 Histone Acetylation -- 1.2.2.2 Histone Methylation -- 1.2.2.2.1 Histone Methylation at Lysines -- 1.2.2.2.2 Histone Methylation at Arginines -- 1.2.3 Histone Phosphorylation -- 1.2.4 Chromatin Binding Proteins -- 1.2.5 Epigenetics and Development -- 1.2.6 Epigenetics and Cancer -- 1.3 Anatomy of a Gene Promoter -- 1.3.1 DNA Elements -- 1.3.2 DNA-binding Proteins -- 1.3.3 Co-regulatory Proteins -- 1.4 Methodology -- 1.4.1 Functional Methods -- 1.4.1.1 Reconstituted Transcription Systems -- 1.4.1.2 Cell Culture Models -- 1.4.1.3 Whole-animal Models -- 1.4.1.4 Transgenic Animals -- 1.4.1.5 Cell-based Knockout Strategies -- 1.4.2 Structural Methods -- 1.4.2.1 Chromatin Immunoprecipitation Assays -- 1.4.2.2 Microarray Technology -- 1.4.2.3 Next Generation Sequencing -- 1.4.2.4 Proteomics -- 1.4.2.5 Bioinformatics and Computational Biology -- 1.5 Transcriptional Control of Gastrointestinal Peptides -- 1.6 Post-Transcriptional Processing -- 1.6.1 Polyadenylation -- 1.6.2 RNA Splicing -- 1.6.2.1 The Spliceosome -- 1.6.2.2 Alternative Splicing -- 1.6.2.3 Regulated Post-transcriptional Mechanisms - mRNA Stability -- 1.6.2.4 Regulated Post-transcriptional Mechanisms - microRNAs -- 1.7 Transport Across the Nuclear Membrane -- 1.8 Concluding Remarks -- Acknowledgments -- References.

2. Post-translational Processing of Gastrointestinal Peptides -- 2.1 Introduction -- 2.2 Translation and Passage into the Endoplasmic Reticulum -- 2.2.1 The Ribosome -- 2.2.2 Protein Folding in the Cytosol -- 2.2.3 The Signal Recognition Particle -- 2.3 Processing in the Endoplasmic Reticulum -- 2.3.1 Signal Peptidase Removal -- 2.3.2 Protein Folding in the ER -- 2.3.3 Disulfide Bond Formation -- 2.3.4 Asparagine-linked N-Glycosylation -- 2.3.5 Acylation -- 2.4 Sorting to the Golgi -- 2.5 Processing in the Golgi -- 2.5.1 Serine- or Threonine-linked O-Glycosylation -- 2.5.2 Sulfation -- 2.5.3 Phosphorylation -- 2.6 Sorting to the Secretory Vesicle -- 2.7 Processing in the Secretory Vesicle -- 2.7.1 Acetylation -- 2.7.2 Di-basic Cleavage -- 2.7.3 Mono-basic Cleavage -- 2.7.4 Aminopeptidase Cleavage -- 2.7.5 Glutaminyl Cyclase -- 2.7.6 Carboxypeptidase Cleavage -- 2.7.7 Amidation -- 2.8 Examples of Processing -- 2.8.1 Progastrin-releasing Peptide -- 2.8.2 Progastrin -- 2.8.3 Sonic Hedgehog -- 2.9 Summary -- References -- 3. Genetic Tools in Gastrointestinal Diseases -- 3.1 The Genetic Architecture of Mendelian and Non-Mendelian Diseases -- 3.2 Genome-Wide Association Studies -- 3.2.1 Common Disease, Common Variant Hypothesis -- 3.2.2 Disease Pathways, Population Differences, and Genetic Architecture of Complex Diseases -- 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 -- 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.

4.3.1 Signaling Through Phospholipase C: Ca2+ Fluxes and Protein Kinase C -- 4.3.2 GPCR Signaling Through PKD -- 4.3.3 GPCR-induced ERK Activation: PKC-dependent and -independent Pathways -- 4.3.4 GPCR Signaling Through EGFR Transactivation -- 4.3.5 GPCR Signaling Through mTOR/p70S6K Activation -- 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 -- 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 -- 5.3.1 Gene Knockouts -- 5.3.2 Knock-in Mice -- 5.4 Promoters Used to Study Gastrointestinal Functions -- 5.5 Genetic Mouse Models for Studies of Normal Gastrointestinal Function -- 5.5.1 Esophagus -- 5.5.2 Stomach -- 5.5.3 Intestine -- 5.6 Genetic Mouse Models of Gastrointestinal Diseases -- 5.6.1 Esophagus -- 5.6.2 Stomach -- 5.6.3 Intestine -- 5.7 Conclusion -- References -- 6. Gastrointestinal Peptides: Gastrin, Cholecystokinin, Somatostatin, and Ghrelin -- 6.1 General Overview -- 6.2 Gastrin -- 6.2.1 Overview -- 6.2.2 Gene Structure and Regulation of Expression -- 6.2.3 Prohormone Processing -- 6.2.4 Peptide Sorting -- 6.2.5 Regulation of Peptide Secretion -- 6.2.6 Receptors and Signal Transduction -- 6.2.6.1 Cloning -- 6.2.6.2 Gene Structure -- 6.2.6.3 CCK2 Receptor -- 6.2.6.4 CCK2L Receptor -- 6.2.6.5 CCK2i4sv Receptor -- 6.2.6.6 ΔCCK2 Receptor -- 6.2.6.7 Regulation of CCK2 Receptor Expression -- 6.2.7 Biological and Physiological Actions -- 6.2.7.1 Acid Secretion -- 6.2.7.2 Mucosal Proliferation and Cellular Maturation.

6.2.7.3 Modulation of Immune Cell Function -- 6.3 Cholecystokinin -- 6.3.1 Overview -- 6.3.2 Gene Structure and Regulation of Expression -- 6.3.3 Prohormone Processing -- 6.3.4 Regulation of Peptide Secretion Release -- 6.3.5 Receptors and Signal Transduction -- 6.3.6 Biological and Physiologic Actions -- 6.3.6.1 Pancreas -- 6.3.6.2 Gallbladder -- 6.3.6.3 Gastric Emptying and Food Intake -- 6.3.6.4 Inflammation -- 6.4 Somatostatin -- 6.4.1 Overview -- 6.4.2 Gene Structure and Regulation of Expression -- 6.4.3 Prohormone Processing -- 6.4.4 Regulation of Peptide Secretion -- 6.4.5 Receptors and Signal Transduction -- 6.4.6 Biological and Physiologic Actions -- 6.4.6.1 Stomach -- 6.4.6.2 Small Bowel -- 6.4.6.3 Colon -- 6.4.6.4 Pancreas -- 6.4.7 Pathological Conditions -- 6.4.7.1 Helicobacter pylori Infection -- 6.4.7.2 Schistosomiasis -- 6.4.7.3 Diabetes Mellitus -- 6.4.7.4 Neuroendocrine Tumors of the GI Tract and Pancreas -- 6.4.7.5 Other Clinical Uses of SST Analogs -- 6.5 Ghrelin -- 6.5.1 Overview -- 6.5.2 Gene Structure and Regulation of Expression -- 6.5.3 Prohormone Processing -- 6.5.4 Regulation of Peptide Secretion -- 6.5.5 Receptors and Signal Transduction -- 6.5.6 Biological and Physiologic Actions -- 6.5.7 Pathological Conditions -- 6.6 Concluding Remarks -- References -- 7. Postpyloric Gastrointestinal Peptides -- 7.1 Secretin -- 7.1.1 Introduction -- 7.1.2 Structure -- 7.1.3 Gastrointestinal Localization of Secretin -- 7.1.4 Secretin Receptor -- 7.1.5 Actions on the Gastrointestinal Tract -- 7.1.6 Regulation of Secretin Secretion -- 7.1.7 Pathobiology of Secretin -- 7.2 Intestinal Somatostatin -- 7.2.1 Gastrointestinal Localization of Somatostatin -- 7.2.2 Somatostatin Receptors -- 7.2.3 Regulation of Somatostatin Secretion -- 7.2.4 Actions on the Gastrointestinal Tract -- 7.3 Vasoactive Intestinal Polypeptide and Related Peptides.

7.3.1 Introduction -- 7.3.2 Structure -- 7.3.3 Gastrointestinal Localization of VIP -- 7.3.4 VIP Receptors -- 7.3.5 Actions on the Gastrointestinal Tract -- 7.3.6 Regulation of VIP Secretion -- 7.3.7 VIP-related Peptides -- 7.3.7.1 Pituitary Adenylate Cyclase Activating Peptide -- 7.3.7.2 Peptide Histidine Isoleucine/Peptide Histidine Methionine -- 7.4 Neurotensin -- 7.4.1 Introduction -- 7.4.2 Structure -- 7.4.3 Gastrointestinal Localization of Neurotensin -- 7.4.4 Neurotensin Receptors -- 7.4.5 Actions on the Gastrointestinal Tract -- 7.4.6 Regulation of Neurotensin Secretion -- 7.5 Neuropeptide Y -- 7.5.1 Introduction -- 7.5.2 Structure -- 7.5.3 NPY Receptors -- 7.5.4 Gastrointestinal Localization of NPY -- 7.5.5 Secretion -- 7.5.6 Actions on the Gastrointestinal Tract -- 7.6 Motilin -- 7.6.1 Introduction -- 7.6.2 Structure -- 7.6.3 Motilin Receptor -- 7.6.4 Gastrointestinal Localization of Motilin -- 7.6.5 Actions on the Gastrointestinal Tract -- 7.6.6 Mechanism of Action -- 7.6.7 Regulation of Motilin Secretion -- 7.6.8 Pathophysiology -- 7.6.9 Erythromycin and Motilides -- 7.7 Peptide YY -- 7.7.1 Introduction -- 7.7.2 Structure -- 7.7.3 Gastrointestinal Localization of PYY and Developmental Appearance of Intestinal PYY -- 7.7.4 PYY Receptors -- 7.7.5 Actions on the Gastrointestinal Tract -- 7.7.6 Regulation of PYY Secretion -- 7.7.7 Neural Control of PYY Release -- 7.7.8 Trophic Actions of PYY on the Gastrointestinal Tract -- 7.7.9 Inhibitory Action of PYY (3-36) on Appetite and Food Intake and Other Metabolic Actions of PYY -- 7.7.10 Pathophysiology of PYY -- 7.8 Conclusions -- References -- 8. Growth Factors in the Gastrointestinal Tract -- 8.1 Introduction -- 8.1.1 Growth Factors Defined -- 8.1.2 Compartmentalization of Growth Factor Function in the Gastrointestinal Tract -- 8.1.3 "Redundancy" in Growth Factor Families.

8.2 TGF-β Family of Peptides and Receptors.