Membrane transporters as drug targets:
Gespeichert in:
| Weitere Verfasser: | |
|---|---|
| Format: | Buch |
| Sprache: | English |
| Veröffentlicht: |
New York [u.a.]
Plenum Press
1999
|
| Schriftenreihe: | Pharmaceutical biotechnology
12 |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | Includes bibliographical references and index |
| Beschreibung: | XXV, 528 S. Ill., graph. Darst. |
| ISBN: | 0306460947 |
Internformat
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| 245 | 1 | 0 | |a Membrane transporters as drug targets |c ed. by Gordon L. Amidon ... |
| 264 | 1 | |a New York [u.a.] |b Plenum Press |c 1999 | |
| 300 | |a XXV, 528 S. |b Ill., graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 490 | 0 | |a Pharmaceutical biotechnology |v 12 | |
| 500 | |a Includes bibliographical references and index | ||
| 700 | 1 | |a Amidon, Gordon L. |4 edt | |
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Datensatz im Suchindex
| _version_ | 1804138794690019328 |
|---|---|
| adam_text | Contents
Chapter 1
Overview of Membrane Transport 1
Doo-Man Oh and Gordon L. Amidon
1. Introduction 1
2. Modes of Membrane Transport 3
2.1. Passive Diffusion 5
2.2. Ion Channels 6
2.3. Facilitated Diffusion 9
2.4. Active Transporters 10
2.5. Secondary Active Transporters 12
2.6. Macromolecular and Bulk Transport 12
3. Energetics of Membrane Transport 12
4. Kinetics of Membrane Transport 13
4.1. Kinetic Equation 13
4.2. Transport Experiments 16
5. Analysis of Membrane Transport 18
6. Methods in Membrane Transport Research 18
6.1. Patch Clamping 19
6.2. Fluorescence Digital Imaging Microscopy 20
6.3. Confocal Microscopy 21
6.4. Reconstitution 21
6.5. Expression in Xenopus laevis Oocytes 21
6.6. Cultured Cells 22
6.7. Electrophysiological Study of Epithelial Transport 23
6.8. Other Commonly Used Experimental Methods 24
7. Summary 24
References 24
XV
xvi Contents
Chapter 2
Classification of Membrane Transporters
Wolfgang Sadee, Richard C. Graul, and Alan Y. Lee
1. Introduction 29
2. Classification of Transporters by Function and Substrate Specificity .. 30
3. A Genomics View of Transporters 32
4. Pharmacogenomics of Transporters 35
5. Evolution of Membrane Transporters; Sequence Analysis 36
6. Selected Examples of Membrane Transporters 39
6.1. HVDipeptide Symporters 40
6.2. Facilitative Glucose Transporters and Related Sequences 44
6.3. Sodium/Glucose and Sodium/Nucleoside Cotransporters 45
6.4. Amino Acid Transporters 48
6.5. Sodium/Neurotransmitter Symporters 49
6.6. ATP-Binding Transport Protein Family 50
7. Conclusion 52
References 53
Chapter 3
Drug Transport and Targeting: Intestinal Transport
Doo-Man Oh, Hyo-kyung Han, and Gordon L. Amidon
1. Introduction 59
2. Intestinal Transporters 60
2.1. General Description of Intestinal Transporters 60
2.2. Peptide Transporter 64
2.3. Nucleoside Transporter 65
2.4. Sugar Transporter 66
2.5. Bile Acid Transporter 66
2.6. Amino Acid Transporters 67
2.7. Organic Anion Transporters 67
2.8. Vitamin Transporters 68
2.9. Phosphate Transporter 68
2.10. Bicarbonate Transporter 69
2.11. Organic Cation Transporter 69
2.12. Fatty Acid Transporter 69
2.13. P-Glycoprotein 69
Contents xvii
3. Prodrugs: Targeting Intestinal Transporters 70
4. Disorders Related to Intestinal Transporters 75
4.1. Water and Electrolyte Transporters 75
4.2. Sugar Transporters 76
4.3. Amino Acid Transporters 76
4.4. Bile Acid Transporter 76
4.5. Vitamin Transporters 77
5. Summary 77
References 78
Chapter 4
The Molecular Basis for Hepatobiliary Transport of Organic Cations
and Organic Anions
Dirk K. F. Meijer, Johan W. Smit, Guido J. E. J. Hooiveld,
Jessica E. van Montfoort, Peter L. M. Jansen, and Michael Miiller
1. Introduction 89
2. Candidate Proteins for Carrier-Mediated Hepatic Uptake
of Cationic Drugs 93
3. Candidate Proteins Involved in Bile Canalicular Transport
of Cationic Drugs 97
3.1. The Cation/Proton Antiport Secretory/Reabsorptive System ... 97
3.2. The mdrl-Type P-Glycoprotein Secretory System 99
3.3. Other ABC Transport Proteins in the Canaliculus that May
Accommodate Cationic Drugs 103
4. Organic Cation Transport in the Intact Liver and Its
Short-Term Regulation 104
5. Substrate Specificity, Driving Forces, and Multiplicity
of Canalicular Organic Cation Carriers 105
6. Relation between Chemical Structure and Clearance via Bile,
Urine, and Intestine 107
7. Molecular Aspects of Organic Cation Transport
and Further Perspectives Ill
8. Hepatic Uptake of Organic Anions: Role of Specific
and Polyspecific Transport Proteins 112
8.1. Na+/Taurocholate Cotransporter (NTCP) 113
8.2. Polyspecific Organic Anion Transport Proteins (OATPs) 115
9. Transport across the Canalicular Membrane: Role
of ABC Transport Proteins 116
xviii Contents
9.1. MDR3 P-Glycoprotein 116
9.2. Homologues of the Multidrug-Resistance Protein MRP 1 118
9.3. Canalicular Bile Salt Transporter (cBST/sPgp) 120
10. Recent Results from Cholestatic Animal Models 121
Appendix: Molecular Features of Currently Identified Carrier Proteins
Involved in Sinusoidal Uptake and Canalicular Transport
of Organic Cations and Anions 122
References 140
Chapter 5
Affinity of Drugs to the Different Renal Transporters for Organic Anions
and Organic Cations: In Situ Ki Values
Karl Julius Ullrich
1. Introduction 159
2. Location of the Transport Processes and Transporters
in the Proximal Renal Tubule 160
3. Transport Processes for Net Reabsorption and Net Secretion 162
4. General Information about the Kt Values Given Here 169
5. Interaction with Contraluminal PAH Transporter 170
6. Interaction with the Contraluminal Sulfate
and Dicarboxylate Transporters 171
7. Interaction with the Three Organic Cation Transporters 171
8. Bi- and Poly substrates: Drugs which Interact Both with Transporters
for Organic Anions and Transporters for Organic Cations 172
9. Conclusions and Perspectives 173
References 173
Chapter 6
Drug Disposition and Targeting: Transport across the Blood-Brain Barrier
Bertrand Rochat and Kenneth L. Audus
1. Introduction 181
2. Permeability of the Blood-Brain Barrier 183
2.1. Carrier-Mediated Transport 183
2.2. Transcytosis 190
3. Summary and Future Perspectives 193
References 193
Contents xjx
Chapter 7
The Mammalian Facilitative Glucose Transporter (GLUT) Family
Michael J. Seatter and Gwyn W. Gould
1. Introduction 201
2. Background 202
3. The Structure of the GLUTs 203
3.1. Predicted Secondary Structure of GLUT 1 203
3.2. Evidence in Favor of the Secondary Structure Model 204
3.3. Biophysical Investigation of GLUT1 204
4. The Dynamics of Glucose Transport 205
4.1. The Alternating Conformation Model 206
4.2. Oligomerization of GLUT1 208
5. Transporter Photoaffinity Labeling 209
6. The Tissue-Specific Distribution of Glucose Transporters 211
6.1. GLUT1 211
6.2. GLUT2 212
6.3. GLUT3 216
6.4. GLUT4 218
6.5. GLUT5 219
7. Recent Work and Future Directions 220
References 221
Chapter 8
Cationic Amino Acid Transporters (CATs): Targets for the Manipulation
of NO-Synthase Activity?
Ellen I. Closs and Petra Graf
1. Introduction 229
2. Identification of Four Related Carrier Proteins for Cationic
Amino Acids in Mammalian Cells 231
2.1. Murine CAT-Proteins (mCATs) 231
2.2. Human CAT-Proteins (hCATs) 233
3. Transport Properties of the CAT Proteins 233
3.1. Substrate Specificity of the mCAT Proteins 234
3.2. Kinetics of mCAT-Mediated Transport 235
3.3. hCAT-Mediated Transport 236
4. CATs and Known Transport Systems for Cationic Amino Acids 237
5. Expression of the CAT Proteins in NO-Producing Cells 239
6. L-Arginine Transport and NO Synthesis 241
xx Contents
7. Conclusions 243
References 244
Chapter 9
Electrophysiological Analysis of Renal Na+-Coupled
Divalent Anion Transporters
Ian Forster, Jiirg Biber, and Heini Murer
1. Introduction 251
2. Steady-State Electrophysiological Characteristics 253
2.1. Recording Pj-Induced Currents from the Xenopus Oocyte 253
2.2. Dose and Voltage Dependence of Steady-State Kinetics 254
2.3. Sodium Slippage in the Absence of Pj 256
2.4. The Order of Substrate Binding and Voltage Dependence
Based on Steady-State Kinetics 256
3. Pre-Steady-State Electrophysiological Characteristics 256
3.1. General Properties of Pre-Steady-State Relaxations 256
3.2. .Voltage Dependence of Pre-Steady-State Relaxations 258
3.3. Estimation of Transporter Number and Turnover 260
3.4. The Effects of Substrates on Pre-Steady-State Kinetics 260
4. A Kinetic Scheme for Na+-Coupled P; Cotransport 262
4.1. The Sequential, Alternating Access Model
for Type II Na+/P; Cotransport 262
4.2. Site of Interaction of Protons and Foscarnet
with Type II Na 7P; Cotransporters 263
5. Conclusions 264
References 265
Chapter 10
Dipeptide Transporters
Ken-ichi Inui and Tomohiro Terada
1. Introduction 269
2. Brush-Border Membrane Transport 270
2.1. Small Peptides 270
2.2. Peptide-like Drugs 271
3. Transcellular Transport 272
3.1. Caco-2 Cell Monolayers 272
3.2. Peptide Transporter in Apical Membranes 273
3.3. Peptide Transporter in Basolateral Membranes 273
4. Cloning of Peptide Transporters 274
Contents xxj
4.1. Structure 274
4.2. Tissue Distribution 276
4.3. Substrate Specificity and Recognition 276
4.4. Structural Features 278
5. Application to Drug Delivery 281
6. Summary and Perspective 283
References 283
Chapter 11
Antigenic Peptide Transporter
Vashti G. Lacaille and Matthew J. Androlewicz
1. Introduction 289
2. TAP and the MHC Class I Antigen Processing Pathway 290
2.1. Introduction 290
2.2. Current Model of MHC Class I Antigen Processing 291
3. TAP Structure and Function 293
3.1. TAPSubstrate Specificity 294
3.2. Characterization of the TAP Peptide-Binding Site 297
4. Viral Inhibition of TAP 297
4.1. Herpes Simplex Virus ICP47 Protein 298
4.2. Human Cytomegalovirus US6 Protein 300
5. TAP as a Drug Target 301
5.1. Peptidomimetics 301
5.2. Synthesis of a TAP Inhibitor 302
5.3. Steric Requirements for Peptide Binding to TAP 303
5.4. Incorporation of Reduced Peptide Bonds and D-Amino Acids
into TAP Substrates 303
5.5. Allosteric Modulation of TAP Activity 305
6. Concluding Remarks 305
References 306
Chapter 12
Nucleoside Transporters of Mammalian Cells
Carol E. Cass, James D. Young, Stephen A. Baldwin, Miguel A. Cabrita,
Kathryn A. Graham, Mark Griffiths, Lori L. Jennings, John R. Mackey,
Amy M. L. Ng, Mabel W. L. Ritzel, Mark F. Vickers, and Sylvia Y. M. Yao
1. Introduction 314
1.1. Overview 314
xxii Contents
1.2. The Heterogeneity of Nucleoside Transport Processes 316
1.3. Recent Advances in the Molecular Biology
of Nucleoside Transporters 318
2. The ENT Family of Nucleoside Transporters 321
2.1. Molecular and Functional Characteristics of the ENT Family .. 321
3. The CNT Family of Nucleoside Transporters 327
3.1. Molecular and Functional Characteristics of the CNT Family . . 327
4. Orphan Nucleoside Transporters 332
4.1. Na+-Dependent Transporters 333
4.2. Organellar Transporters 335
5. Nucleoside Transporters as Drug Targets 336
5.1. Purinergic Receptors and Nucleoside Transporters 336
5.2. Anticancer Drugs and Nucleoside Transporters 338
6. Summary 343
References 344
Chapter 13
Multidrug-Resistance Transporters
Jeffrey A. Silverman
1. Introduction 353
2. MDR Gene Family 354
3. P-Glycoprotein Is an ABC Family Transporter 355
4. Structure of P-Glycoprotein 356
5. MDR] P-gp Is a Pump of Cytotoxic Drugs 356
6. P-Glycoprotein Is an ATP-Dependent Pump 358
7. MDR2 P-gp Is a Phospholipid Transporter 359
8. MDR] Tissue Distribution 359
9. Expression of P-gp in Human Cancer 360
10. MDR2 Tissue Distribution 361
11. Modulation of P-Glycoprotein 361
12. P-Glycoprotein in Drug Absorption and Disposition 364
13. Role of P-gp in Normal Tissues and Drug Disposition 365
13.1. Intestine 365
13.2. Liver 367
13.3. Kidney 368
13.4. Blood-Brain Barrier 368
14. The Multidrug Resistance-Associated Protein 370
15. Tissue Distribution of MRP Expression 370
16. MRP Is an ATP-Dependent Drug Transporter 371
Contents xxiii
17. Modulation of MRP-Mediated Resistance 372
18. Additional Multidrug-Resistance Proteins 373
18.1. Additional MRP Homologues 373
18.2. Lung Resistance Protein 373
19. Summary 374
References 374
Chapter 14
Transporters for Bile Acids and Organic Anions
Hiroshi Suzuki and Yuichi Sugiyama
1. Introduction 387
2. Transport across the Sinusoidal Membrane 388
2.1. Na+-Dependent Transport 388
2.2. Na+-Independent Transport 396
3. Transport across the Canalicular Membrane 403
3.1. Transport of Bile Acids across the Bile Canalicular Membrane . 404
3.2. Transport of Organic Anions across the Bile
Canalicular Membrane 407
4. Concluding Remarks 424
References 424
Chapter 15
Molecular and Functional Characteristics of Cloned Human Organic
Cation Transporters
MarkJ. Dresser, Lei Zhang, and Kathleen M. Giacomini
1. Introduction 441
2. Background 442
3. Molecular Characteristics 447
4. Functional Characteristics of Cloned Transporters 451
4.1. Expression Systems 451
4.2. Functional Methods 455
4.3. Functional Characteristics of the Cloned Human Organic Cation
Transporters 458
5. Tissue Distribution 461
6. Future Studies 463
7. Conclusions 466
References 466
xxiv Contents
Chapter 16
Organic Anion Transporters
Akira Tsuji and Ikumi Tamai
1. Introduction 471
2. Monocarboxylate Transporters in Intestine and Brain 473
2.1. Molecular Characterization of MCT1 and MCT2 473
2.2. Intestinal Transport of Lactate and Short-Chain Fatty Acids
via MCT1 473
2.3. Transport of Weak Organic Acids by MCT1 474
2.4. Monocarboxylate Transport via MCT1
at the Blood-Brain Barrier 475
2.5. Anion Exchange Transport of Monocarboxylates 476
3. Organic Anion Transporters in Liver and Kidney 478
3.1. Organic Anion Transporters in Liver 479
3.2. Organic Anion Transporters in Kidney 482
3.3. Organic Anion Transporters in Other Tissues 483
4. Conclusion 485
References 485
Chapter 17
Vitamin B12 Transporters
Gregory J. Russell-Jones and David H. Alpers
1. Introduction 493
2. General Mechanism of Dietary Absorption of Vitamin B12 495
3. Structure and Biology of the VB|2 Transport Proteins 495
3.1. Haptocorrin (He Cobalophilin, R-Binders, R Protein,
Nonintrinsic Factor) 495
3.2. Intrinsic Factor 499
3.3. Intrinsic Factor Receptor 502
3.4. Transcobalamin II 504
3.5. Transcobalamin II Receptor 505
3.6. Cell Models of Vitamin B |2 Transport 507
4. The Use of Vitamin B12 for Transport of Pharmaceuticals 508
4.1. Conjugation of Vitamin B|2 to Peptides and Proteins 508
4.2. In Vitro Transport of Peptides and Proteins Linked to VB12 .... 509
4.3. In Vivo Transport of Peptides and Proteins Linked to VB,2 .... 509
Contents xxv
4.4. VB]2-Mediated Oral Delivery of Nanoparticles 511
5. Summary 512
References 513
Index 521
|
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| indexdate | 2024-07-09T21:33:51Z |
| institution | BVB |
| isbn | 0306460947 |
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| spelling | Membrane transporters as drug targets ed. by Gordon L. Amidon ... New York [u.a.] Plenum Press 1999 XXV, 528 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Pharmaceutical biotechnology 12 Includes bibliographical references and index Amidon, Gordon L. edt HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=017294087&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Membrane transporters as drug targets |
| title | Membrane transporters as drug targets |
| title_auth | Membrane transporters as drug targets |
| title_exact_search | Membrane transporters as drug targets |
| title_full | Membrane transporters as drug targets ed. by Gordon L. Amidon ... |
| title_fullStr | Membrane transporters as drug targets ed. by Gordon L. Amidon ... |
| title_full_unstemmed | Membrane transporters as drug targets ed. by Gordon L. Amidon ... |
| title_short | Membrane transporters as drug targets |
| title_sort | membrane transporters as drug targets |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=017294087&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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