Georges Vauquelin, Bengt von Mentzer

G Protein-Coupled Receptors

Molecular Pharmacology from Academic Concept to Pharmaceutical Research

• Gebundenes Buch

Produktbeschreibung

G protein-coupled receptors (GPCRs) are membrane proteins that transduce a vast array of extracellular signals into intracellular reactions ranging from cell-cell communication processes to physiological responses. They play an important role in a variety of diseases from cancer and diabetes, to neurodegenerative, inflammatory and respiratory disorders. GPCRs are therefore of utmost interest in drug development: over half of all prescription drugs currently on the market act by targeting these receptors directly or indirectly.

G Protein-coupled Receptors - Molecular Pharmacology provides a clear summary of the current knowledge in this fast-evolving field. The book sets out with an introduction tosignalling molecules and their receptors, and an overview of the technical approaches used to investigate these interactions. Structural, functional and especially pharmacological aspects of GPCRs are then discussed in more detail and much attention is devoted to the analysis andinterpretation of experimental data. The now widespread use of recombinant cell lines, receptor mutants and related artifices in drug research is critically evaluated. Special attention is also devoted to topical but often poorly understood concepts, such as insurmountable antagonism, inverse agonism and allosteric interactions. By combining general information with the major state-of-the-art concepts in GPCR research, the book equips the reader with the necessary background for understanding and critically evaluating the current literature.

Written by two experts from academia and industry, G Protein-coupled Receptors -Molecular Pharmacology offers a unique view of academic and applied approaches aiming to reveal new ideas in pharmaceutical research.
The book will be of interest to anyone involved in drug development and preclinical research and those who need to function within multi-disciplinary teams in the pharmaceutical industry: from investigators to product managers or clinicians who seek to have a broad mechanistic understanding of drug-receptor interactions. Final year undergraduate and postgraduate students in pharmacology and cell and molecular biology will also find the book an invaluable resource.

Produktdetails

• Verlag: Wiley & Sons
• 1. Auflage
• Seitenzahl: 264
• Erscheinungstermin: 1. Dezember 2007
• Englisch
• Abmessung: 253mm x 177mm x 19mm
• Gewicht: 705g
• ISBN-13: 9780470516478
• ISBN-10: 047051647X
• Artikelnr.: 22990956

Autorenporträt

Georges Vauquelin. Department of Molecular and Biochemical Pharmacology, Free University Brussels (VUB), Belgium Bengt von Mentzer. Department of Molecular Pharmacology, AstraZeneca Inc, Sweden

Inhaltsangabe

FOREWORD A) CHEMICAL MESSENGERS AND THE CELL MEMBRANE A.1. Endocrine
signalling by hormones. A.2. The nervous system and synaptic signalling by
neurotransmitters. SMALL MOLECULE NEUROTRANSMITTERS NEUROPEPTIDES A.3.
Paracrine signalling by local chemical messengers. A.4. Hydrophobicity:
effect on release and transport of messengers. A.5. Membrane proteins and
membrane receptors. A.6. Ligand receptor interactions. B) RADIOLIGAND
BINDING STUDIES B.1. Technical aspects of radioligand binding. B.2.
Saturation binding. B.3. Competition binding. B.5. Regional distribution of
receptors. C) FUNCTIONAL STUDIES C.1. Dose-response curves and associated
problems. C.2. From receptor-occupation to stimulus and response. FROM
RECEPTOR OCCUPATION TO STIMULUS FROM STIMULUS TO RESPONSE : LINEAR
RELATIONSHIP FROM STIMULUS TO RESPONSE: NON-LINEAR RELATIONSHIP C.3.
Receptor classification and antagonist affinity. C.4. Pharmacological
models. D) G PROTEIN-COUPLED RECEPTORS D.1. From receptor to response:
introduction to GPCRs. D.2. GPCR structure. D.3. Ligand interaction with
family A, B, C receptors. LIGAND INTERACTION WITH FAMILY A RECEPTORS LIGAND
INTERACTION WITH FAMILY B RECEPTORS LIGAND INTERACTION WITH FAMILY C
RECEPTORS D.4. Receptor activation. D.5. Activated GPCRs: interaction with
G proteins. TECHNIQUES TO STUDY G -PROTEIN COUPLING PREFERENCE DIVERGENCE
OF INTRACELLULAR SIGNALLING D.6. Activated GPCRs: phosphorylation and
internalisation. RECEPTOR PHOSPHORYLATION b-ARRESTIN BINDING MEDIATE GPCR
ENDOCYTOSIS. MECHANISMS TO TERMINATE SIGNALLING. D.7. b-Arrestin- binding
and MAP kinase activation. D.8. GPCR dimerisation and association with
other proteins. INTRODUCTORY COMMENTS GPCR DIMERISATION. GPCR INTERACTION
WITH OTHER MEMBRANE RECEPTORS. GPCR INTERACTION WITH OTHER MEMBRANE
PROTEINS. GPCR INTERACTION WITH CYTOPLASMIC PROTEINS D.9. Early models for
GPCR activation. D.10. Restricted GPCR mobility and G protein coupling.
MEMBRANE COMPARTIMENTALISATION RESTRICTED GPCR- G PROTEIN COUPLING:
EFFECTOR ACTIVITY D.11. Spontaneous receptor- G protein coupling. MODELS
INVERSE AGONISM D.12. Interaction of two G proteins with one activated
receptor state. FUSION PROTEINS BETWEEN GPCRS AND G PROTEINS D.13. Multiple
receptor conformations. "AGONIST TRAFFICKING": WHAT DO MODELS PREDICT?
EXPERIMENTAL "EVIDENCE" FOR AGONIST TRAFFICKING: POTENTIAL PITFALLS
MULTISTATE RECEPTORS: LIGAND- MEDIATED SEQUENTIAL CHANGES IN RECEPTOR
CONFORMATION MULTIPLE RECEPTOR STATES RELATED TO TRUNCATION, COVALENT
MODIFICATION AND MUTATION D.14. Multistate receptors and multiple ligand
binding sites. THE GENERAL ALLOSTERIC TERNARY COMPLEX MODEL EXOGENOUS AND
ENDOGENOUS ALLOSTERIC MODULATORS ALLOSTERIC PHENOMENA AT GPCR: DETECTION BY
RADIOLIGAND BINDING DETECTION OF ALLOSTERIC PHENOMENA AT GPCR BY FUNCTIONAL
ASSAYS USEFULNESS OF ALLOSTERIC MODULATORS D.15. "Competitive",
"non-competitive "and "insurmountable" antagonism. CO-INCUBATION, NO
RECEPTOR RESERVE ANTAGONIST PREINCUBATION, NO RECEPTOR RESERVE D.16.
Naturally occurring mutations of GPCRs. E) CONCLUDING REMARKS REFERENCES
INDEX