Studies of membrane transporters have had a great impact on our understanding of human diseases and the design of effective drugs. In Membrane Transporters in Drug Discovery and Development: Methods and Protocols, expert researchers provide practical methodologies of the ongoing research on membrane transporters, considering applications of transporter technologies in drug discovery and development. Chapters include new and useful fields and methodologies, including pharmacogenomics, nutrigenomics, systems biology, bioinformatics, nuclear magnetic resonance (NMR), imaging, and quantitative real-time-PCR. Transporter studies in drug discovery and development for various diseases are discussed, including neuropsychiatric disorders, cardiovascular diseases, ophthalmic diseases, cancer, and diabetes. Composed in the highly successful Methods in Molecular Biology™ series format, each chapter contains a brief introduction, step-by-step methods, a list of necessary materials, and a Notes section which shares tips on troubleshooting and avoiding known pitfalls.
Wide-ranging and current, Membrane Transporters in Drug Discovery and Development: Methods and Protocols delivers a collection of practical protocols that can be used immediately in the lab, along with critical surveys of key topics by leading researchers in the field.
Table of Contents1. Membrane Transporters and Drug Development: Relevance
to Pharmacogenomics, Nutrigenomics, Epigenetics, and Systems Biology
2. Bioinformatics for Transporter Pharmacogenomics and Systems Biology:
Data Integration and Modeling with UML
3. Multidrug Resistance: Phylogenetic Characterization of Superfamilies
of Secondary Carriers that Include Drug Exporters
4. Targeting Drug Transporters – Combining In Silico and In Vitro
Approaches to Predict In Vivo
5. Methods to Evaluate Transporter Activity in Cancer
6. Analysis of Expression of Drug Resistance-Linked ABC Transporters
in Cancer Cells by Quantitative RT-PCR
7. Fluorescence Studies of Drug Binding and Translocation
by Membrane Transporters
8. A Model for Transport Studies of the Blood–Brain Barrier
9. Genetic Variants in the Vesicular Monoamine Transporter 1
(VMAT1/SLC18A1) and Neuropsychiatric Disorders
10. Equilibrium Binding and Transport by Vesicular Acetylcholine Transporter
11. ABC Transporters in Ophthalmic Disease
12. Imaging of Protein Translocation In Situ in Skeletal Muscle of Living Mice
13. Glucose Transporters in Parasitic Protozoa
14. NMR Studies of Membrane Proteins
15. Site-Directed Mutagenesis in the Study of Membrane Transporters
16. Xenopus laevis Oocytes
17. Measurement of Intracellular pH
18. Measurement of Plasma Membrane Calcium–Calmodulin-Dependent
ATPase (PMCA) Activity
19. Assessment of the Contribution of the Plasma Membrane Calcium
ATPase, PMCA, Calcium Transporter to Synapse Function Using Patch
Clamp Electrophysiology and Fast Calcium Imaging