Drug efficacy at G protein-coupled receptors

Annual Review of Pharmacology and Toxicology

Volumn 42, Issue , 2002, Pages 349-379

  Kenakin, Terry ^a  

^a GLAXOSMITHKLINE   (United States)

Author keywords

Efficacy; G protein coupled receptors; GPCRs; Receptor models; Receptor theory

Indexed keywords

4 (1,1 DIMETHYLHEPTYL) 1',2',3',4',5',6' HEXAHYDRO 2,3' DIHYDROXY 6' (3 HYDROXYPROPYL)BIPHENYL; ANANDAMIDE; BETA 2 ADRENERGIC RECEPTOR; BETA 2 ADRENERGIC RECEPTOR BLOCKING AGENT; BETA 2 ADRENERGIC RECEPTOR STIMULATING AGENT; CANNABINOID RECEPTOR; CHEMOKINE RECEPTOR CCR5; CHOLECYSTOKININ RECEPTOR; CHOLECYSTOKININ RECEPTOR BLOCKING AGENT; DEXANABINOL; DICHLORISOPRENALINE; DIMER; DOPAMINE 2 RECEPTOR; G PROTEIN COUPLED RECEPTOR; GUANINE NUCLEOTIDE BINDING PROTEIN; HYPOPHYSIS ADENYLATE CYCLASE ACTIVATING POLYPEPTIDE RECEPTOR; ISOPRENALINE; LIGAND; MEMBRANE PROTEIN; OLIGOMER; RANTES; SUBSTANCE P DERIVATIVE; TETRAHYDROCANNABINOL;

DRUG CONFORMATION; DRUG EFFICACY; DRUG RECEPTOR BINDING; GENOTYPE; HUMAN; INTERNALIZATION; LIGAND BINDING; NONHUMAN; OLIGOMERIZATION; PHENOTYPE; PLEIOTROPY; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; RECEPTOR AFFINITY; RECEPTOR DOWN REGULATION; RECEPTOR OCCUPANCY; REVIEW;

ANIMALS; DIMERIZATION; GENOTYPE; GTP-BINDING PROTEINS; HUMANS; LIGANDS; MATHEMATICS; PHENOTYPE; PHOSPHORYLATION; PROTEIN CONFORMATION; RECEPTORS, CELL SURFACE;

EID: 0036177114     PISSN: 03621642     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev.pharmtox.42.091401.113012     Document Type: Review

References (164)

1. Affinity and intrinsic activity in the theory of competitive inhibition
2. A modification of receptor theory
3. The many faces of G protein signaling
4. Selectivity in signal transduction determined by γ subunits of heterotrimeric G proteins
5. Differential effects of CC chemokines on CC chemokine receptor 5 (CCR5) phosphorylation and identification of phosphorylation sites on the CCR5 carboxy terminus
6. Endocytosis and recycling of G-protein-coupled receptors
7. Regulatory mechanisms that modulate signaling by G-protein-coupled receptors
8. Antagonist-stimulated internalization of the G protein-coupled cholecystokinin receptor
9. A RANTES, MIP-1α, MIP-1β receptor as a fusion co-factor for macrophage-tropic HIV-1
10. Expression cloning of new receptors used by simian and human immunodeficiency viruses
11. Chemokine receptor utilization by human immunodeficiency virus type 1 isolates that replicate in microglia
12. Will multiple co-receptors need to be targeted by inhibitors of human immunodeficiency virus type 1 entry?
13. Chemokine receptorsthe new frontier for aids research
14. Potential inhibition of HIV-1 infectivity in macrophages and lymphocytes by a novel CCR5 antagonist
15. HIV co-receptor down-regulation as an antiviral principle: SDF-1 alpha-dependent internalization of the chemokine receptor CXCR4 contributes to inhibition of HIV replication
16. Aminooxypentane-RANTES induces CCR5 internalization but inhibits recycling: A novel inhibitory mechanism of HIV infectivity
17. Similarities and differences in RANTES- and (AOP)-RANTES-triggered signals: Implications for chemotaxis
18. Hinges, swivels and switches: The role of prolines in signaling via transmembrane α-helices
19. Constitutive activation of the α 1B-adrenergic receptor by all amino acid substitutions at a single site
20. 1B-adrenergic receptor: Potential role of protonation and hydrophobicity of a highly conserved aspartate
21. The use of β-haloalkylamines in the differentiation of receptors and in the determination of dissociation constants of receptor-agonist complexes
22. The binding potential, a neglected linkage concept
23. Allosteric linkage
24. Ligand binding and internal equilibria in proteins
25. A mutation-induced activated state of the β2-adrenergic receptor: Extending the ternary complex model
26. The cubic ternary complex receptor-occupancy model. I. Model description
27. The cubic ternary complex receptor-occupancy model. II. Understanding apparent affinity
28. The cubic ternary complex receptor-occupancy model. III. Resurrecting efficacy
29. Role of G-protein subunits in transmembrane signaling
30. Signal sorting and amplification through G-protein coupled receptors
31. G-proteins in signal transduction
32. 1B-adrenergic receptor signal-inactivating point mutation
33. Antagonists with negative intrinsic activity at δ-opioid receptors coupled to GTP-binding proteins
34. Calculation of diffusion-limited kinetics for the reactions in collision coupling and receptor cross-linking
35. Mechanistic model of G-protein signal transduction: Determinants of efficacy and the effect of pre-coupled receptors
36. Timing is everything: The role of kinetics in G-protein activation
37. Structure-based calculation of the equilibrium folding pathway of proteins: Correlation with hydrogen exchange protection factors
38. The structural distribution of cooperative interactions in proteins: Analysis of the native state ensemble
39. Hydrogen exchange in proteins
40. Hydrogen exchange and the dynamic structure of proteins
41. Structural description of acid-denatured cytochrome c by hydrogen exchange and 2D NMR
42. Protein folding intermediates: Native-state hydrogen exchange
43. Experimental study of the protein folding landscape: Unfolding reactions in cytochrome c
44. Structural mechanisms for domain movements in proteins
45. Forces and factors that contribute to the structural stability of membrane proteins
46. Essential dynamics of protein
47. Conformational substates in proteins
48. The energy landscapes and motions of proteins
49. On the nature of allosteric transitions: A plausible model
50. Can allosteric regulation be preditcted from structure?
51. Model systems for the study of seven-transmembrane-segment receptors
52. Structure and function of G protein-coupled receptors
53. Specificity of receptor G-protein interactions: Searching for the structure behind the signal
54. Three cytoplasmic loops of rhodopsin interact with transducin
55. Multisite contacts involved in coupling of the β-adrenergic receptor with the stimulatory guanine-nucleotide-binding regulatory protein
56. Constitutive activity of receptors coupled to guanine nucleotide regulatory proteins
57. Fluorescent labeling of purified β2-adrenergic receptor: Evidence for ligand specific conformational changes
58. Activation of the α1b-adrenergic receptor is initiated by disruption of an interhelical salt bridge constraint
59. Structural instability of a constitutively active G-protein coupled receptor
60. Enhanced myocardial function in transgenic mice over-expressing the β2-adrenergic receptor
61. Physiological effects of inverse agonists in transgenic mice with myocardial over-expression of the β2-adrenoceptor
62. 2+ current in mouse ventricular myocytes
63. Contribution of serine residues to constitutive and agonist-induced signaling via the D2s dopamine receptor: Evidence for multiple, agonist-specific active conformations
64. Amino acids 356-372 constitute a Gi-activator sequence of the α2-adrenergic receptor and have a Phesubstitute in the G-protein-activator sequence motif
65. i-proteins. Comparisons of their contributions to GTPase activity and signal transduction and analysis of receptor G-protein activation stoichiometry
66. i coupling
67. 2-adrenergic receptor determines subtype-specific coupling to cAMP production
68. Gi activator region of α2A-adrenergic receptors: Distinct basic residues mediate Gi versus Gs activation
69. Identification of a conserved switch residue responsible for selective constitutive activation of the β2-adrenergic receptor
70. Genetic evidence for involvement of multiple effector systems in α2A-adrenergic receptor inhibition of stimulus-secretion coupling
71. Constitutive activation of a single effector pathway: Evidence for multiple activation states of a G-protein coupled receptor
72. Agonist-receptor efficacy I: Mechanisms of efficacy and receptor promiscuity
73. Agonist-receptor efficacy II: Agonist-trafficking of receptor signals
74. Agonist-specific receptor conformations
75. Opioid receptors are coupled tightly to G-proteins but loosely to adenylate cyclase in NG108-15 cell membranes
76. Differential signal transduction by five splice variants of the PACAP receptor
77. Comparative effects of receptor inactivation, 17β-estradiol and pertussis toxin on dopaminergic inhibition of prolactin-secretion in vitro
78. Agonist-specific coupling of a cloned Drosophila octopamine/tyramine receptor to multiple second messenger systems
79. 11]SP analogues
80. Molecular analysis of β2-adrenoceptor coupling to Gs-, Gi-, and Gq-proteins
81. i/10 activation profiles in CHO cells expressing human muscarinic acetylcholine receptors: Dependence on agonist as well as receptor-subtype
82. Effect pathway-dependent relative efficacy at serotonin type 2A and 2C receptors: Evidence for agonist-directed trafficking of receptor stimulus
83. Dual activation and inhibition of adenylyl cyclase by cannabinoid receptor agonists: Evidence for agonist-specific trafficking of intracellular process
84. Pharmacological proteus?
85. The classification of seven transmembrane receptors in recombinant receptor systems
86. Protean agonists: Keys to receptor-active states?
87. Differences between natural and recombinant G-protein coupled receptor systems with varying receptor/G-protein stoichiometry
88. Inverse, protean, and ligand-selective agonism: Matters of receptor conformation
89. From the static to the dynamic
90. Inverse agonist activity of β-adrenergic antagonists
91. 2-adrenergic receptor
92. The use of stimulus-biased assay systems to detect agonist-specific receptor active-states: Implications for the trafficking of receptor stimulus by agonists
93. Signal transduction by calcitonin: Multiple ligands, receptors, and signaling pathways
94. s complex: Evidence for agonist-specific states
95. s interactions: Evidence for multiple receptor conformations
96. Agonist selective receptor states: The new level of selectivity?
97. Beta adrenergic kinase. Activity of partial agonists for stimulation of adenylate cyclase correlates with the ability to promote receptor phosphorylation
98. μ opioid receptor phosphorylation, desensitization, and ligand efficacy
99. Homologous desensitization of the D1 dopamine receptor
100. Agonist-induced desensitization of D1-dopamine receptors linked to adenyl cyclase in cultured NS20Y neuroblastoma cells
101. Modeling activation and desensitization of G-protein coupled receptors provides insight into ligand efficacy
102. Agonist-induced phosphorylation of the angiotensin II (AT1A) receptor requires generation of a conformation that is distinct from the inositol phosphate-signaling state
103. 5]enkephalin-mu-opioid complexes demonstrated by cyclic independent protein kinase phosphorylation
104. Differential opioid agonist regulation of the mouse μ opioid receptor
105. Selection of distinct conformational states of the 5-HT3 receptor by full and partial agonists
106. Phorbol esters and SDF-1 induce rapid endocytosis and down-regulation of the chemokine receptor CXCR4
107. Viral quasispecies and the problem of vaccine-escape and drug resistant mutants
108. Relative replicative fitness of zidoviudine-resistant human immunodeficiency virus type 1 isolates in vitro
109. T-cell-line-tropic human immunodeficiency virus type 1 that is made resistant to stromal cell-derived factor 1-α contains mutations in the envelope gp 120 but does not show a switch in coreceptor use
110. Morphine activates opioid receptors without causing their rapid internalization
111. The CB1 cannabinoid receptor juxtamembrane C-terminal peptide confers activation to specific G-proteins in brain
112. Ligand-induced phosphorylation, clustering, and desensitization of A1 adenosine receptors
113. Evidence for adenosine/dopamine receptor interactions: Indications for heterodimerization
114. Dimerization of the δ opioid receptor
115. Opioids and their complicated receptor complexes
116. 2-adrenergic receptor transmembrane domain inhibits both receptor dimerization and activation
117. 2-adrenergic receptor dimerization in living cells using bioluminescence resonance energy transfer (BRET)
118. Subtypes of the somatostatin receptor assemble as functional and heterodimers
119. Dimerization of the extracellular calciumsensing receptor (CaR) on the cell surface of CaR-transfected HEK293 cells
120. Intermolecular interactions between dimeric calcium-sensing receptor monomers are important for its normal function
121. Disulfide bonds in the extracellular calcium-polyvalent cation-sensing receptor correlate with dimer formation and its response to divalent cations in vitro
122. Molecular aspects of muscarinic receptor dimerization
123. Phosphorylation and palmitoylation of the human D2L dopamine receptor in sf9 cells
124. Desensitization, phosphorylation and palmitoylation of the human dopamine D1 receptor
125. Dopamine D2 receptor dimers and receptor-blocking peptides
126. Oligomerization of dopamine and serotonin receptors
127. Dopamine D2 receptor dimers in human and rat brain
128. Dimerization of 8-OHDPAT increases activity at serotonin 5-HT1A receptors
129. Serotonin 5-HT1B and 5-HT1D receptors form homodimers when expressed alone and heterodimers when co-expressed
130. Human serotonin 1B receptor expression in sf9 cells: Phosphorylation, palmitoylation, and denylyl cyclase inhibition
131. Mechanism of transdominant inhibition of CCR-5 mediated HIV-1 infection by ccr5 Δ32
132. B receptor
133. B receptors-the first 7TM heterodimers
134. Receptors for dopamine and somatostatin: Formation of hetero-oligomers with enhanced functional activity
135. G-protein-coupled receptor heterodimerization modulates receptor function
136. Cooperation of multiple CCR5 co-receptors is required for infections by human immunodeficiency virus type 1
137. Beyond receptor expression: The influence of receptor conformation, density, and affinity in HIV-1 infection
138. Subtypes of κ-opioid receptor: Fact or fiction
139. δ-opioid receptor subtypes and cross talk with μ receptors
140. Retention of supraspinal delta-like analgesia and loss of morphine tolerance in delta opioid receptor knockout mice
141. Delta and kappa opioid receptors are differentially regulated by dynamindependent endocytosis when activated by the same alkaloid agonist
142. Kappa opioid receptor endocytosis by dynorphin peptides
143. U59-488H-induced internalization of the human k opioid receptor involves B-arrestin and dynamindependent mechanism
144. 4-adrenoceptor" in mammalia heart
145. 1-adrenergic receptor
146. 3-adrenergic-independent effects of CGP 12177 in brown adipose tissue
147. Factors determining specificity of signal transduction by G-protein coupled receptors
148. Species differences in A1 adenosine/G-protein coupling: Identification of a membrane protein that stabilizes the association of the receptor/G-protein complex
149. RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor
150. The amino terminus of receptor activity modifying proteins is a critical determinant of glycosylation state and ligand binding of calcitonin-like receptor
151. RAMPS: Accessory proteins for seven transmembrane domain receptors
152. Multiple amylin receptors arise from receptor activity modifying protein interaction with the calcitonin receptor gene product
153. Pharmacological characterization of receptor-activity-modifying proteins (RAMPs) and the human calcitonin receptor
154. Expression cloning and receptor pharmacology of human calcitonin receptors from MCF-7 cells and their relationship to amylin receptors
155. Use of constitutive G-protein coupled receptor activity for drug discovery
156. Imprecision in presentation of binding studies
157. Efficacy in drug receptor theory: Outdated concept or under-valued tool?
158. Commentary: The measurement of efficacy in the drug discovery agonist selection process