Pharmacology of intestinal permeation

著者

• Csáky, T. Z.

書誌事項

Pharmacology of intestinal permeation

editor, T. Z. Csáky

（Handbook of experimental pharmacology, v. 70）

Springer-Verlag, 1984

• pt. 1 : us
• pt. 2 : us
• pt. 1 : gw
• pt. 2 : gw

注記

Includes bibliographies and indexes

内容説明・目次

巻冊次

pt. 1 : gw ISBN 9783540131007

内容説明

The intestine, particularly the small bowel, represents a large surface (in the adult 2 human approximately 200m ) through which the body is exposed to its environment. A vigorous substrate exchange takes place across this large surface: nutrients and xenobiotics are absorbed from the lumen into the bloodstream or the lymph, and simultaneously, the same types of substrate pass back into the lumen. The luminal surface of the intestine is lined with a "leaky" epithelium, thus the passage of the substrates, in either direction, proceeds via both transcellular and intercellular routes. Simple and carrier-mediated diffusion, active transport, pinocytosis, phagocytosis and persorption are all involved in this passage across the intestinal wall. The term "intestinal permeation" refers to the process of passage of various substances across the gut wall, either from the lumen into the blood or lymph, or in the opposite direction. "Permeability" is the condition of the gut which governs the rate of this complex two-way passage. The pharmacologist's interest in the problem of intestinal permeation is twofold: on the one hand, this process determines thebioavailability of drugs and contributes significantly to the pharmacokinetics and toxicokinetics of xeno- biotics; on the other hand, the pharmacodynamic effects of many drugs are manifested in a significant alteration of the physiological process of intestinal permeation.

目次

1 Morphology of the Intestinal Mucosa..- A. Introduction.- I. General Considerations.- II. Heterogeneity of Intestinal Epithelium.- B. Morphological Techniques.- C. The Mucosal Interface.- I. Surface Morphology of Small Intestine.- II. Surface Morphology of Large Intestine.- D. The Enterocyte.- I. The Striated Border.- II. The Apical Cell Coat and Cell Membrane.- III. The Cores of Microvilli and the Terminal Web.- IV. Other Enterocyte Surfaces.- V. The Enterocyte Cytoplasm.- VI. The Precursor Cells of the Crypt and Epithelial Dynamics.- VII. Special Features of Large Bowel Enterocytes.- E. Other Cell Types of Intestinal Mucosa.- I. Goblet Cells.- II. Intestinal Endocrine Cells.- III. Paneth Cells.- IV. Tuft Cells.- V. M Cells.- VI. Intraepithelial Lymphocytes.- VII. Globule Leukocytes.- F. Deeper Layers of the Intestine.- I. Lamina Propria.- II. Muscle Layers and Their Autonomic Innervation.- III. The Serosa.- G. Conclusion.- References.- 2 Intestinal Permeation and Permeability: an Overview..- A. Introduction.- B. Diffusion Processes.- C. The Intestine.- D. Passage of Substances Across Biologic Membranes.- I. Simple Diffusion.- II. Specific Transport Mechanisms.- III. Persorption.- E. Intestinal Permeation.- References.- 3 Permeability and Related Phenomena: Basic Concepts.- A. Introduction.- B. Passive Transport of Nonelectrolytes in Solution.- I. Nonequilibria Determining a Passive Net Flux.- II. Kinetics of Polar Solute Passage Driven by a Concentration Difference.- III. Kinetics of Nonpolar Solute Passage Driven by a Concentration Difference.- IV. Calculation of the Relative Values of the Permeability Coefficients of a Substance Across Two Membranes in Series.- C. Passive Transport of Univalent Electrolytes.- I. Kinetics of the Passive Net Transport off Univalent Electrolytes Across a Porous Membrane.- II. Transmembrane Potentials.- III. Transepithelial Potentials.- D. Transport Across Biological Membranes.- I. Passive Transport of Polar Nonelectrolytes Through Biological Membranes.- II. Passive Transport of Polar Electrolytes Through Biological Membranes.- E. Passive Transport by Carrier Facilitation.- I. Kinetics of Carrier-facilitated Transport.- II. Calculation of the Apparent Affinity Constant.- III. Saturation Kinetics.- IV. Substrate Competition.- V. Countertransport.- F. Passive Transport of Water.- I. Driving Forces.- II. The Hydrophilic Pores and Their Radius.- III. The Reflection Coefficient of Staverman.- IV. Solvent Drag.- G. Active Transport.- I. Identification.- II. Dependence of Water Transport on Metabolism.- III. Countercurrent Exchange.- IV. Thermodynamic Efficiency.- References.- 4 Methods for Investigation of Intestinal Permeability.- A. Introduction.- B. In Vivo Techniques.- I. In Conscious Animals.- II. In Anesthetized Animals.- C. In Vitro Techniques.- I. Isolated Loops.- D. Modifications of the Permeant.- I. Artificial Sugar Compounds.- II. Artificial Amino Acid Analogs.- III. Radioisotopes.- References.- 5 Vascular Perfusion of Rat Small Intestine for Permeation and Metabolism Studies.- A. Introduction.- B. Isolated Intestine with Lymph Collection.- I. Historical Aspects.- II. Development of Procedure.- III. Description of Procedure.- IV. Evidence for Sustained Viability.- V. Perfusate Composition During Recirculation.- VI. Applications.- C. Autoperfused Intestinal Segment In Vivo.- I. Description of Basic Procedure.- II. Specialized Techniques and Adaptations.- III. Applications.- D. Concluding Remarks.- I. Advantages of the Isolated Intestinal Preparation.- II. Advantages of the Autoperfused Intestinal Preparation.- References.- 6 The Use of Isolated Membrane Vesicles in the Study of Intestinal Permeation.- A. Introduction.- B. Methods for Membrane Isolation.- I. Brush Border Membranes.- II. Basolateral Plasma Membranes.- III. Enzyme and Polypeptide Content of Isolated Brush Border and Basolateral Membranes.- IV. Morphology and Orientation of Isolated Brush Border and Basolateral Membranes.- C. Methods for Analysing Transport Properties of Isolated Membrane Vesicles.- D. Transport Studies ..- I. Systems Involved in Primary Active Transport.- II. Systems Involved in Secondary Active Transport.- E. Energetics and Kinetics.- F. Studies with Isolated Membrane Vesicles on the Physiological Regulation of Transepithelial Transport.- G. Conclusions.- References.- 7 The Transport Carrier Principle.- A. The Carrier Concept in Relation to Intestinal Transport.- I. Early Development of the Carrier Concept.- B. The Kinetic Approach to Membrane Carriers.- I. The Simple Pore and Simple Carrier.- II. Coupled Transport Systems.- III. Chemiosmotic Coupling.- C. The Thermodynamics and Energetics of Membrane Carrier Systems.- I. Carrier Asymmetry.- II. Energetics of Countertransport Systems.- III. Energetics of Cotransport.- References.- 8 Energetics of Intestinal Absorption.- A. Introduction.- B. Special Fuels as Sources of Energy.- C. Membrane Transport and Oxidative Phosphorylation.- D. General Features of Energy Utilization.- E. Basal Energy Requirements of Tissues.- F. The Energetics of Absorption Are the Energetics of Movement Along a Multistep Pathway.- G. Variable Patterns of Fuels Available to the Small Intestine.- H. Intestinal Metabolism of Nutrients During Absorption.- I. Energetics of Brush Border Transport Processes.- K. Influence off Circulation of Epithelial Transport: General Principles.- I. Convective Transport.- II. Cellular Transport: Influence of Vascular Flow on Power Requirements.- III. A Simple Model.- L. Effects of Circulation on Epithelial Transport in the Steady State.- M. Influence of Circulation on Wash-out from Epithelium.- N. Influence of Circulation on Sodium Fluxes Across Vascularly Perfused Intestine.- I. Na Fluxes Across the Small Intestine.- II. Na Fluxes Across the Colon.- III. Factors Affecting Na Fluxes Across Frog Intestine.- O. Effects of Vascular Flow on Size of Tissue Fluid Compartments.- I. Measurement of Extracellular and Interstitial Space.- II. Influence of Vascular Flow on Permeability of the Pathway Between Epithelium and Blood.- P. Conclusions.- References.- 9 Polarity of Intestinal Epithelial Cells: Permeability of the Brush Border and Basolateral Membranes.- A. Introduction.- B. Functionally Polarized and Unpolarized Cells.- C. The Epithelial Layer as a Selective Barrier.- D. Brush Border Membrane: Morphology, Chemical Composition, and Biochemical Characteristics.- I. Morphology.- II. Chemical Composition.- III. The Brush Border as a Selective Membrane.- E. Basolateral Membrane: Chemical and Biochemical Organization.- I. Chemical Composition.- II. Enzyme Content.- F. Permeability of Brush Border and Basolateral Membranes.- G. Factors Affecting Membrane Permeability.- H. Concluding Remarks.- References.- 10 Electrical Phenomena and Ion Transport in the Small Intestine.- A. Introduction.- B. Transepithelial Electrical Parameters and Ionic Fluxes in the Small Intestine.- I. Ionic Conductance and its Structural and Functional Correlates . 316 II. Ionic Fluxes.- C. Pathways of Ion Transport in the Small Intestine.- I. The Cellular Pathway.- II. The Paracellular Pathway.- D. Analysis of Intestinal Electrical Parameters in Terms of Electrical Equivalent Circuits.- E. Na+-Coupled Transport of Organic Solutes by the Small Intestine.- I. Transepithelial Effects: The Na+ Gradient Hypothesis.- II. Intracellular Effects: The Electrical Potential Profile of the Absorptive Cell.- III. Equivalent Circuit Analysis: Is the Na+/K+ Exchange Pump Rheogenic?.- IV. Transapical Sugar Transport: Energetics and Stoichiometry.- F. The Regulation of Ion Transport in the Small Intestine.- I. Cyclic Nucleotides and Intestinal Transport: Secretion.- G. Conclusion.- References.- 11 Intestinal Permeation of Water.- A. Introduction.- B. Historical Concepts of Intestinal Fluid Absorption.- C. Formal Description of Water Transfer.- I. General Principles.- II. Diffusion.- III. Filtration.- IV. Osmosis.- V. Interaction Between Solute and Solvent Fluxes.- D. Passive Water Transport.- I. Diffusional Water Permeability.- II. Osmotic Water Permeability.- III. Rectification of Osmotic Water Flow.- IV. Route of Diffusional and Osmotic Water Flow.- V. Water Flow Driven by a Hydrostatic Pressure Gradient.- E. Active Water Transport.- I. The Series Membrane Model.- II. Hypertonic Interspace Mechanisms (Local Osmosis Theories) 431 III. Countercurrent Exchanger Model.- F. Relation Between Intestinal Blood Flow and Water Absorption.- G. Conclusion.- References.- 12 Intestinal Permeability to Calcium and Phosphate.- A. Introduction.- B. Calcium Transport.- I. Brush Border Membrane.- II. Basolateral Membranes.- C. Phosphate Transport.- D. Mechanism of Action of 1,25-Dihydroxycholecalciferol.- I. Pharmacology of the Receptors for 1,25-Dihydroxycholecalciferol 479 II. Regulation of Transport Mediated by a Nuclear Action of Vitamin D.- III. Regulation of Lipid Metabolism by Vitamin D.- IV. Calcium Binding Proteins.- V. Membrane-Bound Calcium Binding Protein.- VI. Calcium-Dependent Adenosine Triphosphatase.- VII. Adenylate Cyclase.- E. Vitamin D-Independent Regulation of Intestinal Calcium Absorption.- F. Summary.- References.- 13 Protein-Mediated Epithelial Iron Transfer.- A. Introduction.- B. Mucosal Uptake, Storage, and Transfer of Iron.- I. Experimental Models.- II. Choice of the Experimental Conditions and Iron Test Doses.- III. Molecular Aspects of Iron Absorption: Search for Mucosal Iron Carriers.- IV. Studies in Purified Fractions of Mucosal Epithelium and Mucosal Cell Suspension.- V. Morphological Studies.- C. Regulation of Iron Absorption.- I. The Significance of Mucosal Iron Binding Proteins.- II. Luminal Factors.- D. Heavy Metal Interaction with the Iron Transfer System: Sites of Interaction.- E. Conclusions.- References.- 14 Intestinal Absorption of Heavy Metals.- A. Introduction.- B. Experimental Problems.- C. General Characteristics of Heavy Metal Absorption.- I. Kinetics.- II. Role of Mucosal Metal Retention.- III. Specificity of Absorption Mechanisms.- IV. Chemical Form of Absorbed Metals.- V. Effects of Age.- D. Absorption of Some Individual Metals.- I. Cadmium.- II. Zinc.- III. Lead.- IV. Copper.- V. Mercury.- VI. Other Metals.- E. Summary and Conclusions.- References.- 15 Intestinal Permeability of Water-Soluble Nonelectrolytes: Sugars, Amino Acids, Peptides.- A. General Functions of the Enterocyte.- B. Intestinal Permeability to Sugars.- I. Simple Diffusion.- II. Facilitated Diffusion and Active Transport.- III. Enzymes Related to Sugar Transport.- IV. Sugar Binding Sites.- V. The Role of Brush Border and Basolateral Membranes in Sugar.- Transport.- VI. Energetics of Sugar Transport.- C. Intestinal Permeability to Amino Acids and Peptides.- I. Specific Transport Systems of l- and D-Amino Acids.- II. Interactions Between Amino Acid and Sugar Transport.- III. Absorption and Transport of Peptides.- D. Concluding Remarks.- References.- 16 Pharmacologic Aspects of Intestinal Permeability to Lipids (Except Steroids and Fat-Soluble Vitamins).- A. Introduction.- B. Brief Outline of the Physiology of Intestinal Permeability to Lipids.- I. Permeation from the Intestinal Lumen (Fat Absorption).- II. Permeation from the Plasma Pool (Uptake and Metabolism of Plasma Free Fatty Acids).- C. Mechanisms by which Drugs May Affect the Intestinal Permeability to Lipids.- I. Interference with Intraluminal Events of Fat Absorption.- II. Disturbance of Intestinal Mucosal Integrity.- III. Interference with Intracellular Events of Intestinal Lipid and Lipoprotein Metabolism.- IV. Interactions with Intestinal Metabolism of Plasma Free Fatty Acids.- D. Agents which Affect the Intestinal Permeability to Lipids in a More Complex Manner.- I. Ethanol.- II. Hormones.- III. Cytostatic Agents.- IV. Dietary Fiber.- E. Concluding Remarks.- References.- 17 Intestinal Absorption of the Fat-Soluble Vitamins: Physiology and Pharmacology.- A. Introduction.- B. Lipid Digestion and Absorption.- C. The Fat-Soluble Vitamins.- I. Vitamins A.- II. Vitamins D.- III. Vitamins E.- IV. Vitamins K.- D. Hydrolysis of Esters of the Fat-Soluble Vitamins.- I. Intraluminal Digestion.- II. Membrane Digestion of Fat-Soluble Vitamin Esters.- E. Role of Bile Salts in Fat-Soluble Vitamin Absorption.- F. Route of Transport of Fat-Soluble Vitamins from the Intestine.- I. Lymphatic Route.- II. Portal Venous Route.- G. Enterohepatic Circulation of the Fat-Soluble Vitamins.- H. Intestinal Uptake of the Fat-Soluble Vitamins.- I. Vitamin A.- II. Vitamin D.- III. Vitamin E.- IV. Vitamin K.- V. Absorption of the Ubiquinones.- J. Summary of Intestinal Absorption of Fat-Soluble Vitamins.- K. Nonnutrient Substances which Interfere with Fat-Soluble Vitamin Absorption.- I. Bile Salt Sequestrants.- II. Nonabsorbale Lipids.- III. Drugs Affecting Small Intestinal Mucosal Morphology and Metabolism.- IV. Other Drugs Which Cause Steatorrhoea.- L. Other Effects of Drugs on Fat-Soluble Vitamin Absorption.- M. Summary of Drug Effects on Fat-Soluble Vitamin Absorption.- References.

巻冊次

pt. 2 : gw ISBN 9783540131014

内容説明

The intestine, particularly the small bowel, represents a large surface (in the adult 2 human approximately 200 m ) through which the body is exposed to its environ- ment. A vigorous substrate exchange takes place across this large surface: nutrients and xenobiotics are absorbed from the lumen into the bloodstream or the lymph, and simultaneously, the same types of substrate pass back into the lumen. The luminal surface of the intestine is lined with a "leaky" epithelium, thus the passage of the substrates, in either direction, proceeds via both transcellular and intercellular routes. Simple and carrier-mediated diffusion, active transport, pinocytosis, phagocytosis and persorption are all involved in this passage across the intestinal wall. The term "intestinal permeation" refers to the process of passage of various substances across the gut wall, either from the lumen into the blood or lymph, or in the opposite direction. "Permeability" is the condition of the gut which governs the rate of this complex two-way passage. The pharmacologist's interest in the problem of intestinal permeation is twofold: on the one hand, this process determines the bioavailability of drugs and contributes significantly to the pharmacokinetics and toxicokinetics of xeno- biotics; on the other hand, the pharmacodynamic effects of many drugs are manifested in a signigicant alteration of the physiological process of intestinal permeation.

目次

18 Intestinal Absorption of Xenobiotics..- A. Introduction.- B. Drug Absorption and Pharmacologic Response.- C. The Side of Drug Absorption.- D. The Intestinal Barrier and its Permeability.- I. The Unstirred Water Layer.- II. The Transcellular Route.- III. The Intercellular Route.- IV. Absorption via the Lymph.- E. Factors Which Influence the Intestinal Absorption of Xenobiotics.- I. Factors Inherent to the Drug Molecule.- II. Factors Inherent of Pharmaceutical Formulation.- III. Factors Inherent to Intestinal Permeability.- IV. Factors Inherent to the Patient.- References.- 19 Role of Digestive Enzymes in the Permeability of the Enterocyte.- A. Introduction.- B. Relationship Between the Hydrolytic and Transport Systems of the Enterocytes.- I. The Basic Types of Digestion and Their Relation to Absorption..- II. Membrane Digestion and Digestive-Absorptive Functions of the Enterocyte Membrane.- III. Classification of Digestive Processes.- IV. The Enzyme Apparatus of Membrane Digestion.- V. Membrane Digestion in Normal Function of the Gastrointestinal Tract.- C. Enzyme Apparatus of the Apical Membrane of the Enterocytes.- I. Fine Location of Membrane Hydrolases.- II. The Amphipathic Structure of Membrane Enzymes.- III. Functions of the Hydrophobic Part of Intestinal Enzymes.- IV. Characterization of Hydrolases.- D. Characterization of the Transport of Free Monomers and Hydrolysis-Released Monomers.- I. Comparison of the Rates of Absorption of Oligomers and Monomers.- II. Factors Affecting the Relationship Between Oligomer and Monomer Transport.- III. Kinetic Characteristics of Oligomer and Monomer Transport.- IV. Competitive Interactions Between Free and Hydrolysis-Released Monomers.- V. Role of Na+ in the Transport of Hydrolysis-Released and Free Monomers.- E. The Enzyme Transport Complexes of the Apical Membrane of the Enterocytes.- I. Cooperative Interactions Between Enzymatic and Transport Parts.- II. Allosteric Interactions Between Enzyme and Transport Parts.- III. Possible Molecular Models.- IV. The Permeome.- F. Conclusion.- I. Adaptability and Regulation of the Enzyme Transport Complexes.- II. The Enzyme Transport Complexes of the Membrane in Pathology.- III. Concluding Remarks.- References.- 20 The Surface pH of the Intestinal Mucosa and its Significance in the Permeability of Organic Anions..- A. Introduction.- B. Intestinal pH Measurements.- C. Acidification Studies.- I. The Effect of Mucosal Glucose Concentration.- II. The Involvement of Carbonic Anhydrase.- III. Sodium Ion Exchange Mechanisms.- IV. Hydrogen-Potassium Exchange.- V. Acidification and Electrical Events.- VI. The Mechanism of Hydrogen Ion Secretion.- VII. Hormonal Effects.- VIII. Infectious Agents.- D. The Intestinal Acid Microclimate.- I. Evidence for the Microclimate Hypothesis.- II. Clinical Studies.- III. Related Phenomena.- IV. The Role of Mucus.- E. Alternative Concepts.- I. The Unstirred Layer Hypothesis.- II. Permeation of Ionised Forms.- III. Extraction Theory.- F. Absorption and the Microclimate Hypothesis: Three Paradigms.- I. Folic Acid Absorption.- II. Fatty Acid Absorption.- III. Propranolol Absorption.- G. Modelling the System.- H. Conclusion.- References.- 21 The Role of the Unstirred Water Layer in Intestinal Permeation.- A. Unstirred Water Layers: Historical and Conceptual Background.- B. Water Compartments In and Around the Intestinal Mucosal Cell.- C. Comparison of Dimensions of the Unstirred Water Layer with Morphological Parameters.- D. The Glycocalyx and Mucus as Diffusion Barriers.- E. Intestinal Membrane Structure.- F. Movement of Solutes Across Biologic Membranes: General Principles.- G. Effects of Aqueous Diffusion Barriers on Solute Movement.- H. A Consideration of Surface Areas.- J. Consequences of Failure to Correct for the Unstirred Water Layer and Passive Permeation.- K. Diffusion Barriers of Greater Complexity.- L. Possible Functional Heterogeneity of the Villus.- M. Effect of Carrier Molecules, Solubility of Probe, and Metabolism in the Cytosolic Compartment.- N. Effect of Membrane Polarity on Penetration of Passively Transported Molecules.- O. Anomalous Behavior of Diffusion of Certain Solutes Across the Intestine.- P. Methods Available for the Measurement of the Dimensions of the Unstirred Water Layer.- I. Effective Thickness of the Unstirred Water Layer.- II. Effective Surface Area of the Unstirred Water Layer.- Q. Examples of the Effect of Unstirred Water Layers on Intestinal Transport.- I. Estimates of the Temperature Coefficient.- II. Estimates of Kinetic Constants of Carrier-Mediated Transport..- III. Permeation of Weak Electrolytes: Acid Microclimate.- IV. Effect of Volume Flow, "Sweeping Away" Effects, and Unstirred Layers on the Estimation of Effective Osmotic Pressure Across a Membrane.- V. Membrane "Pores"18 Intestinal Absorption of Xenobiotics..- A. Introduction.- B. Drug Absorption and Pharmacologic Response.- C. The Side of Drug Absorption.- D. The Intestinal Barrier and its Permeability.- I. The Unstirred Water Layer.- II. The Transcellular Route.- III. The Intercellular Route.- IV. Absorption via the Lymph.- E. Factors Which Influence the Intestinal Absorption of Xenobiotics.- I. Factors Inherent to the Drug Molecule.- II. Factors Inherent of Pharmaceutical Formulation.- III. Factors Inherent to Intestinal Permeability.- IV. Factors Inherent to the Patient.- References.- 19 Role of Digestive Enzymes in the Permeability of the Enterocyte.- A. Introduction.- B. Relationship Between the Hydrolytic and Transport Systems of the Enterocytes.- I. The Basic Types of Digestion and Their Relation to Absorption..- II. Membrane Digestion and Digestive-Absorptive Functions of the Enterocyte Membrane.- III. Classification of Digestive Processes.- IV. The Enzyme Apparatus of Membrane Digestion.- V. Membrane Digestion in Normal Function of the Gastrointestinal Tract.- C. Enzyme Apparatus of the Apical Membrane of the Enterocytes.- I. Fine Location of Membrane Hydrolases.- II. The Amphipathic Structure of Membrane Enzymes.- III. Functions of the Hydrophobic Part of Intestinal Enzymes.- IV. Characterization of Hydrolases.- D. Characterization of the Transport of Free Monomers and Hydrolysis-Released Monomers.- I. Comparison of the Rates of Absorption of Oligomers and Monomers.- II. Factors Affecting the Relationship Between Oligomer and Monomer Transport.- III. Kinetic Characteristics of Oligomer and Monomer Transport.- IV. Competitive Interactions Between Free and Hydrolysis-Released Monomers.- V. Role of Na+ in the Transport of Hydrolysis-Released and Free Monomers.- E. The Enzyme Transport Complexes of the Apical Membrane of the Enterocytes.- I. Cooperative Interactions Between Enzymatic and Transport Parts.- II. Allosteric Interactions Between Enzyme and Transport Parts.- III. Possible Molecular Models.- IV. The Permeome.- F. Conclusion.- I. Adaptability and Regulation of the Enzyme Transport Complexes.- II. The Enzyme Transport Complexes of the Membrane in Pathology.- III. Concluding Remarks.- References.- 20 The Surface pH of the Intestinal Mucosa and its Significance in the Permeability of Organic Anions..- A. Introduction.- B. Intestinal pH Measurements.- C. Acidification Studies.- I. The Effect of Mucosal Glucose Concentration.- II. The Involvement of Carbonic Anhydrase.- III. Sodium Ion Exchange Mechanisms.- IV. Hydrogen-Potassium Exchange.- V. Acidification and Electrical Events.- VI. The Mechanism of Hydrogen Ion Secretion.- VII. Hormonal Effects.- VIII. Infectious Agents.- D. The Intestinal Acid Microclimate.- I. Evidence for the Microclimate Hypothesis.- II. Clinical Studies.- III. Related Phenomena.- IV. The Role of Mucus.- E. Alternative Concepts.- I. The Unstirred Layer Hypothesis.- II. Permeation of Ionised Forms.- III. Extraction Theory.- F. Absorption and the Microclimate Hypothesis: Three Paradigms.- I. Folic Acid Absorption.- II. Fatty Acid Absorption.- III. Propranolol Absorption.- G. Modelling the System.- H. Conclusion.- References.- 21 The Role of the Unstirred Water Layer in Intestinal Permeation.- A. Unstirred Water Layers: Historical and Conceptual Background.- B. Water Compartments In and Around the Intestinal Mucosal Cell.- C. Comparison of Dimensions of the Unstirred Water Layer with Morphological Parameters.- D. The Glycocalyx and Mucus as Diffusion Barriers.- E. Intestinal Membrane Structure.- F. Movement of Solutes Across Biologic Membranes: General Principles.- G. Effects of Aqueous Diffusion Barriers on Solute Movement.- H. A Consideration of Surface Areas.- J. Consequences of Failure to Correct for the Unstirred Water Layer and Passive Permeation.- K. Diffusion Barriers of Greater Complexity.- L. Possible Functional Heterogeneity of the Villus.- M. Effect of Carrier Molecules, Solubility of Probe, and Metabolism in the Cytosolic Compartment.- N. Effect of Membrane Polarity on Penetration of Passively Transported Molecules.- O. Anomalous Behavior of Diffusion of Certain Solutes Across the Intestine.- P. Methods Available for the Measurement of the Dimensions of the Unstirred Water Layer.- I. Effective Thickness of the Unstirred Water Layer.- II. Effective Surface Area of the Unstirred Water Layer.- Q. Examples of the Effect of Unstirred Water Layers on Intestinal Transport.- I. Estimates of the Temperature Coefficient.- II. Estimates of Kinetic Constants of Carrier-Mediated Transport..- III. Permeation of Weak Electrolytes: Acid Microclimate.- IV. Effect of Volume Flow, "Sweeping Away" Effects, and Unstirred Layers on the Estimation of Effective Osmotic Pressure Across a Membrane.- V. Membrane "Pores"18 Intestinal Absorption of Xenobiotics..- A. Introduction.- B. Drug Absorption and Pharmacologic Response.- C. The Side of Drug Absorption.- D. The Intestinal Barrier and its Permeability.- I. The Unstirred Water Layer.- II. The Transcellular Route.- III. The Intercellular Route.- IV. Absorption via the Lymph.- E. Factors Which Influence the Intestinal Absorption of Xenobiotics.- I. Factors Inherent to the Drug Molecule.- II. Factors Inherent of Pharmaceutical Formulation.- III. Factors Inherent to Intestinal Permeability.- IV. Factors Inherent to the Patient.- References.- 19 Role of Digestive Enzymes in the Permeability of the Enterocyte.- A. Introduction.- B. Relationship Between the Hydrolytic and Transport Systems of the Enterocytes.- I. The Basic Types of Digestion and Their Relation to Absorption..- II. Membrane Digestion and Digestive-Absorptive Functions of the Enterocyte Membrane.- III. Classification of Digestive Processes.- IV. The Enzyme Apparatus of Membrane Digestion.- V. Membrane Digestion in Normal Function of the Gastrointestinal Tract.- C. Enzyme Apparatus of the Apical Membrane of the Enterocytes.- I. Fine Location of Membrane Hydrolases.- II. The Amphipathic Structure of Membrane Enzymes.- III. Functions of the Hydrophobic Part of Intestinal Enzymes.- IV. Characterization of Hydrolases.- D. Characterization of the Transport of Free Monomers and Hydrolysis-Released Monomers.- I. Comparison of the Rates of Absorption of Oligomers and Monomers.- II. Factors Affecting the Relationship Between Oligomer and Monomer Transport.- III. Kinetic Characteristics of Oligomer and Monomer Transport.- IV. Competitive Interactions Between Free and Hydrolysis-Released Monomers.- V. Role of Na+ in the Transport of Hydrolysis-Released and Free Monomers.- E. The Enzyme Transport Complexes of the Apical Membrane of the Enterocytes.- I. Cooperative Interactions Between Enzymatic and Transport Parts.- II. Allosteric Interactions Between Enzyme and Transport Parts.- III. Possible Molecular Models.- IV. The Permeome.- F. Conclusion.- I. Adaptability and Regulation of the Enzyme Transport Complexes.- II. The Enzyme Transport Complexes of the Membrane in Pathology.- III. Concluding Remarks.- References.- 20 The Surface pH of the Intestinal Mucosa and its Significance in the Permeability of Organic Anions..- A. Introduction.- B. Intestinal pH Measurements.- C. Acidification Studies.- I. The Effect of Mucosal Glucose Concentration.- II. The Involvement of Carbonic Anhydrase.- III. Sodium Ion Exchange Mechanisms.- IV. Hydrogen-Potassium Exchange.- V. Acidification and Electrical Events.- VI. The Mechanism of Hydrogen Ion Secretion.- VII. Hormonal Effects.- VIII. Infectious Agents.- D. The Intestinal Acid Microclimate.- I. Evidence for the Microclimate Hypothesis.- II. Clinical Studies.- III. Related Phenomena.- IV. The Role of Mucus.- E. Alternative Concepts.- I. The Unstirred Layer Hypothesis.- II. Permeation of Ionised Forms.- III. Extraction Theory.- F. Absorption and the Microclimate Hypothesis: Three Paradigms.- I. Folic Acid Absorption.- II. Fatty Acid Absorption.- III. Propranolol Absorption.- G. Modelling the System.- H. Conclusion.- References.- 21 The Role of the Unstirred Water Layer in Intestinal Permeation.- A. Unstirred Water Layers: Historical and Conceptual Background.- B. Water Compartments In and Around the Intestinal Mucosal Cell.- C. Comparison of Dimensions of the Unstirred Water Layer with Morphological Parameters.- D. The Glycocalyx and Mucus as Diffusion Barriers.- E. Intestinal Membrane Structure.- F. Movement of Solutes Across Biologic Membranes: General Principles.- G. Effects of Aqueous Diffusion Barriers on Solute Movement.- H. A Consideration of Surface Areas.- J. Consequences of Failure to Correct for the Unstirred Water Layer and Passive Permeation.- K. Diffusion Barriers of Greater Complexity.- L. Possible Functional Heterogeneity of the Villus.- M. Effect of Carrier Molecules, Solubility of Probe, and Metabolism in the Cytosolic Compartment.- N. Effect of Membrane Polarity on Penetration of Passively Transported Molecules.- O. Anomalous Behavior of Diffusion of Certain Solutes Across the Intestine.- P. Methods Available for the Measurement of the Dimensions of the Unstirred Water Layer.- I. Effective Thickness of the Unstirred Water Layer.- II. Effective Surface Area of the Unstirred Water Layer.- Q. Examples of the Effect of Unstirred Water Layers on Intestinal Transport.- I. Estimates of the Temperature Coefficient.- II. Estimates of Kinetic Constants of Carrier-Mediated Transport..- III. Permeation of Weak Electrolytes: Acid Microclimate.- IV. Effect of Volume Flow, "Sweeping Away" Effects, and Unstirred Layers on the Estimation of Effective Osmotic Pressure Across a Membrane.- V. Membrane "Pores".- VI. Potential Role of the Intestinal Unstirred Water Layer in Disease.- References.- 22 Intestinal Permeation of Organic Bases and Quaternary Ammonium Compounds.- A. Introduction.- B. Absorption of Organic Bases and Quaternary Ammonium Compounds.- I. Dependence on Polarity.- II. Dependence on Concentration.- III. Dependence on Time.- C. Intestinal Secretion of Organic Cations.- I. Secretion by the Isolated Mucosa of Guinea-Pig Small Intestine..- II. Substrate Specificity.- III. Localization of the Secretory System in the Enterocyte.- IV. In Vivo Secretion.- D. A Concept for the Intestinal Permeation of Organic Cations.- E. Comparative Aspects of Organic Cation Secretion.- I. Intestinal Secretion of Other Xenobiotics.- II. Secretion of Organic Cations by Other Organs.- F. Conclusions.- References.- 23 Role of Blood Flow in Intestinal Permeation.- A. Introduction.- B. Methods.- C. Theoretical Considerations.- D. Experimental Data.- I. Dependence of Intestinal Absorption on Total Intestinal Blood Flow Rate.- II. Dependence of Intestinal Absorption on Intramural Blood Flow Pattern.- III. Role of Villous Countercurrent Exchange in Intestinal Absorption.- E. Concluding Remarks.- References.- 24 Hormonal Effects on Intestinal Permeability.- A. Introduction.- B. Gastrin.- I. In Vitro Studies.- II. In Vivo Studies.- C. Cholecystokinin.- D. Vasoactive Intestinal Polypeptide.- I. In Vitro Studies.- II. In Vivo Studies.- III. VIP-Secreting Tumors.- E. Secretin.- F. Insulin.- I. Influence of Exogenous Insulin on Intestinal Permeability.- G. Glucagon.- I. Effect on Intestinal Water and Electrolyte Movements.- II. Endogenous Hyperglucagonemia.- III. Effect on Sugar and Amino Acid Absorption In Vivo.- IV. Effect on Sugar and Amino Acid Transfer In Vitro.- V. Effect on Portal Glucose Transport.- VI. Changes of Mucosal cAMP and cGMP Levels After Glucagon Treatment in the Rat Small Intestine.- VII. Intestinal Mucosal Adaptation to Glucagon.- H. Other Gastrointestinal Polypeptides.- I. Gastric Inhibitory Polypeptide.- II. Pancreatic Polypeptide.- III. Somatostatin.- IV. Sorbin.- J. General Remarks on the Effects of Gastrointestinal Hormones on Intestinal Permeation.- References.- 25 The Influence of Opiates on Intestinal Transport.- A. Introduction.- B. In Vivo Studies.- C. In Vitro Studies.- I. Opiate Receptors.- II. Possible Neural Mediation.- D. Ion Flux Responses.- E. Antisecretory Activity.- F. Summary.- References.- 26 Effect of Cholera Enterotoxin on Intestinal Permeability.- A. Introduction.- B. Cholera Enterotoxin-Intestinal Interaction.- I. The Enterotoxin.- II. Enterotoxin-Enterocyte Interaction.- III. Enterotoxin Activation of Adenylate Cyclase.- IV. Cyclic AMP and Intestinal Secretion.- C. Role of Increased Filtration in the Production of Cholera-Induced Intestinal Secretion.- I. Increased Intestinal Permeability.- II. Increased Driving Force.- D. Conclusion.- References.- 27 Aspects of Bacterial Enterotoxins Other than Cholera on Intestinal Permeability.- A. Introduction.- B. Escherichia coli.- I. Heat-Labile Toxin.- II. Heat-Stable Toxin.- III. Relationship of Surface Adhesion (Colonization Factors) to Fluid Secretion.- IV. Surface Mucosal Invasion (Enteroadherence).- C. Shigella.- D. Prostaglandin Released from Inflamed Tissue and Fluid and Electrolyte Secretion.- E. Salmonella.- I. Salmonella Enteritis.- II. Role of Increased Capillary Hydrostatic Pressure and Transmucosal Permeability.- III. Role for a Salmonella Enterotoxin.- F. Pseudomonas aeruginosa.- G. Campylobacter fetus.- H. Yersinia enterocolitica.- J. Noncoliform Enterobacteriaceae.- I. Klebsiella pneumoniae Toxin.- II. Enterobacter cloacae Toxin.- III. Aeromonas hydrophila Toxin.- K. Food Poisoning Organisms.- I. Bacillus cereus Toxin.- II. Clostridial Toxin.- L. Staphylococcus.- M. Additional Mechanisms for Toxin-Mediated Permeation Defects.- I. Evidence for a Role for Calcium.- II. Filtration Secretion.- References.- 28 Mechanisms of Action of Laxative Drugs.- A. Introduction.- B. Intestinal Tract Smooth Muscle Response to Laxatives.- C. Effects of Laxatives on Fluid and Electrolyte Movement.- I. Cellular and Mucosal Damage.- II. Enhanced Mucosal Permeability.- III. Role of cAMP in the Actions of Laxatives.- IV. Effects of Laxatives on NA+, K+-ATPase and Energy Metabolism.- V. Hormones as Mediators of Laxative Action.- D. Bulk and Dietary Fibers.- I. Water-Retaining Properties.- II. Role of Bacteria in the Action of Bulk Laxatives.- III. Altered Transit Time.- IV. Fiber Interaction.- V. Carbohydrate Laxative Drugs.- E. Summary.- References.- 29 Action Mechanisms of Secretagogue Drugs.- A. Introduction.- B. Theoretical Considerations.- I. Inhibition of Active Absorption.- II. Active Secretion.- III. Filtration.- C. Triarylmethane and Anthraquinone Derivatives.- I. Effect on Intestinal Fluid and Electrolyte Transfer.- II. Chemistry, Structure-Activity Relationship, and Pharmacokinetics.- III. Proposed Action Mechanisms.- IV. Conclusion.- D. Surfactants.- I. Effect on Intestinal Fluid and Electrolyte Transfer.- II. Structure-Activity Relationship.- III. Proposed Action Mechanisms.- IV. Conclusions.- E. General Summary and Concluding Remarks.- References.- 30 Use and Abuse of Cathartics.- A. Introduction.- B. Classification.- I. Bulking Agents.- II. Contact Cathartics.- III. Stool Softeners.- IV. Osmotic Laxatives.- V. Per Rectum Evacuants.- C. Indications for Use.- I. Constipation.- II. The Irritable Bowel Syndrome.- D. Laxative Abuse.- I. Habitual Abuse.- II. Surreptitious Abuse.- E. Summary.- References.- 31 Intestinal Permeability Studies in Humans.- A. Introduction.- B. Methods for Studying Intestinal Permeability in Humans.- I. Intestinal Perfusion.- II. Intestinal Permeability Studied by Test Molecules.- III. Electrical Transmucosal Potential Difference.- C. Permeability Characteristics of the Human Gut.- I. Studies Employing Intestinal Intubation and Perfusion.- II. Selectivity of Cation Permeability.- III. Transcellular Intestinal Permeability.- IV. Unstirred Water Layer and Intestinal Permeability.- V. Intestinal Permeability to Peptide Macromolecules.- VI. Persorption of Particles.- D. Influence of Drugs on Intestinal Permeability.- I. Influence on Electrolyte and Water Transfer.- II. Change in Intestinal Permeability by Cytostatic Treatment.- E. Intestinal Permeability in Disease.- I. Coeliac Disease.- II. Inflammatory Bowel Disease.- References.

「Nielsen BookData」 より

詳細情報

• NII書誌ID(NCID): BA10154864
• ISBN:
  • 0387131000
  • 0387131019
  • 3540131000
  • 3540131019
• LCCN: 84005558
• 出版国コード: gw
• タイトル言語コード: eng
• 本文言語コード: eng
• 出版地: Berlin ; New York
• ページ数/冊数: 2 v.
• 大きさ: 25 cm
• 分類:
  • LCC : QP905
  • LCC : QP156
  • DC19 : 615/.1 s
  • DC19 : 612/.33
• 件名:
  • LCSH : Intestinal absorption
  • LCSH : Gastrointestinal agents -- Physiological effect
  • MESH : Intestinal Absorption
  • MESH : Intestines -- metabolism
  • MESH : Cell Membrane Permeability -- drug effects
  • MESH : Drugs -- metabolism
• 親書誌ID:
  • BA00516120