Efficacy at g-protein-coupled receptors (original) (raw)

• Waud, D. R. Pharmacological receptors. Pharmacol. Rev. 20, 49–88 (1968).
  CAS PubMed Google Scholar
• Colquhoun, D. Binding, gating, affinity and efficacy: the interpretation of structure–activity relationships for agonists and of the effects of mutating receptors. Br. J. Pharmacol. 125, 924–947 (1998).
  Article CAS PubMed Google Scholar
• Kenakin, T. P. & Ross, E. in Goodman and Gilman's The Pharmacological Basis of Therapeutics 10th edn Ch. 2 (eds Hardman, J. G. & Limbird, L. E.) 31–45 (McGraw-Hill, New York, 2001).
  Google Scholar
• Kenakin, T. P. Efficacy in drug receptor theory: outdated concept or under-valued tool? Trends Pharmacol. Sci. 20, 400–405 (1999).
  Article CAS PubMed Google Scholar
• Onaran, H. O. & Costa, T. Agonist efficacy and allosteric models of receptor action. Ann. NY Acad. Sci. 812, 98–115 (1997).
  Article CAS PubMed Google Scholar
• Onaran, H. O., Scheer, A., Cotecchia, S. & Costa, T. in The Pharmacology of Functional, Biochemical, and Recombinant Systems Handbook of Experimental Pharmacology Vol. 148 (eds Kenakin, T. P. & Angus, J. A.) 217–280 (Springer, Heidelberg, 2000).References 5 and 6 outline a new approach to viewing receptor activation as being a process of probability of stabilization of receptor conformations for the expression of biological activity.
  Google Scholar
• Ariens, E. J. Affinity and intrinsic activity in the theory of competitive inhibition. Part I. Problems and theory. Arch. Int. Pharmacodyn. Ther. 99, 32–49 (1954).The first paper to discuss the property of some molecules to induce response as an intrinsic property of the drug–receptor pair and, also, the first to attempt to quantify this property.
  CAS PubMed Google Scholar
• Kenakin, T. P. Prenalterol as a selective cardiostimulant: differences between organ and receptor selectivity. J. Cardiovasc. Pharmacol. 7, 208–210 (1985).
  Article CAS PubMed Google Scholar
• Stephenson, R. P. A modification of receptor theory. Br. J. Pharmacol. 11, 379–393 (1956).Following reference 7 , this work extended the concept of efficacy as being a drug–receptor property. It also introduced the important concept of the non-linear relationships between receptor occupancy, stimulus and response.
  CAS Google Scholar
• Furchgott, R. F. in Advances in Drug Research Vol. 3. (eds Harper, N. J. & Simmonds, A. B.) 21–55 (Academic, London/New York, 1966).This paper described the quantization of efficacy into 'intrinsic efficacy', namely the unit stimulus given to a single receptor by an agonist. This concept enabled comparison of stimuli using receptor systems containing different receptor densities on the cell surface.
  Google Scholar
• Wyman, J. The binding potential, a neglected linkage concept. J. Mol. Biol. 11, 631–667 (1965).
  Article CAS PubMed Google Scholar
• Wyman, J. Allosteric linkage. J. Am. Chem. Soc. 89, 2202–2232 (1967).An important treatise on linkage-theory analysis of the reciprocal allosteric interaction of ligands and proteins.
  Article CAS Google Scholar
• Weber, G. Ligand binding and internal equilibria in proteins. Biochemistry 11, 864–878 (1972).
  Article CAS PubMed Google Scholar
• Weber, G. Energetics of ligand binding to proteins. Adv. Protein Chem. 29, 1–83 (1975).
  Article CAS PubMed Google Scholar
• Rodbell, M. The role of hormone receptors and GTP-regulatory proteins in membrane transduction. Nature 284, 17–22 (1980).
  Article CAS PubMed Google Scholar
• Gilman, A. G. G-proteins: transducers of G-protein generated signals. Annu. Rev. Biochem. 56, 615–645 (1987).
  Article CAS PubMed Google Scholar
• Bourne, H. R. How receptors talk to trimeric G-proteins. Curr. Opin. Cell Biol. 9, 134–142 (1997).
  Article CAS PubMed Google Scholar
• Chen, W.-J. et al. Expression cloning and receptor pharmacology of human calcitonin receptors from MCF-7 cells and their relationship to amylin receptors. Mol. Pharmacol. 52, 1164–1175 (1997).
  Article CAS PubMed Google Scholar
• Kenakin, T. Differences between natural and recombinant G protein-coupled receptor systems with varying receptor/G protein stoichiometry. Trends Pharmacol. Sci. 18, 456–464 (1997).
  Article CAS PubMed Google Scholar
• Watson, C. et al. The use of stimulus-biased assay systems to detect agonist-specific receptor active states: implications for the trafficking of receptor stimulus by agonists. Mol. Pharmacol. 58, 1230–1238 (2000).
  Article CAS PubMed Google Scholar
• Clarke, W. P. & Bond, R. A. The elusive nature of intrinsic efficacy. Trends Pharmacol. Sci. 19, 271–277 (1998).
  Article Google Scholar
• Frauenfelder, H., Parak, F. & Young, R. D. Conformational substrates in proteins. Annu. Rev. Biophys. Biophys. Chem. 17, 451–479 (1988).
  Article CAS PubMed Google Scholar
• Frauenfelder, H., Sligar, S. G. & Wolynes, P. G. The energy landscapes and motions of proteins. Science 254, 1598–1603 (1991).
  Article CAS PubMed Google Scholar
• Hvidt, A. & Nielsen, S. Hydrogen exchange in proteins. Adv. Protein Chem. 21, 287–386 (1966).
  Article CAS PubMed Google Scholar
• Woodward, C. Is the slow-exchange core the protein folding core? Trends Biol. Sci. 18, 359–360 (1993).
  Article CAS Google Scholar
• Woodward, C., Simon, I. & Tuchsen, E. Hydrogen exchange and the dynamic structure of proteins. Mol. Cell. Biochem. 48, 135–160 (1982).
  Article CAS PubMed Google Scholar
• Hilser, V. J. & Freire, E. Structure-based calculation of the equilibrium folding pathway of proteins: correlation with hydrogen exchange protection factors. J. Mol. Biol. 262, 756–772 (1996).
  Article CAS PubMed Google Scholar
• Hilser, V. J. & Freire, E. Predicting the equilibrium protein folding pathway: structure-based analysis of staphylococcal nuclease. Protein Struct. Funct. Genet. 27, 171–183 (1997).
  Article CAS Google Scholar
• Hilser, V. J., Dowdy, D., Oas, T. G. & Freire, E. The structural distribution of cooperative interactions in proteins: analysis of the native state ensemble. Proc. Natl Acad. Sci. USA 95, 9903–9908 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Bai, Y., Sosnick, T. R., Mayne, L. & Englander, S. W. Protein folding intermediates: native-state hydrogen exchange. Science 269, 192–197 (1995).
  Article CAS PubMed Central PubMed Google Scholar
• Milne, J. S., Mayne, L., Roder, H., Wand, A. J. & Englander, S. W. Determinants of protein hydrogen exchange studied in equine cytochrome c. Protein Sci. 7, 739–745 (1998).
  Article CAS PubMed Central PubMed Google Scholar
• Milne, J. S., Xu, Y., Mayne, L. C. & Englander, S. W. Experimental study of the protein folding landscape: unfolding reactions in cytochrome c. J. Mol. Biol. 290, 811–822 (1999).
  Article CAS PubMed Google Scholar
• Ikezu, T., Okamoto, T., Ogata, E. & Nishimoto, I. Amino acids 356–372 constitute a Gi-activator sequence of the α2-adrenergic receptor and have a Phe substitute in the G-protein-activator sequence motif. FEBS Lett. 31, 29–32 (1992).
  Article Google Scholar
• Eason, M. G. & Liggett, S. B. Identification of a Gs coupling domain in the amino terminus of the third intracellular loop of the α2A-adrenergic receptor. Evidence for distinct structural determinants that confer Gs versus Gi coupling. J. Biol. Chem. 270, 24753–24760 (1995).
  Article CAS PubMed Google Scholar
• Nasman, J., Jansson, C. C. & Akerman, K. E. The second intracellular loop of the α2-adrenergic receptor determines subtype-specific coupling to cAMP production. J. Biol. Chem. 272, 9703–9708 (1997).
  Article CAS PubMed Google Scholar
• Burt, A. R. et al. Agonist occupation of an α2A-adrenoceptor–Gi1α fusion protein results in activation of both receptor-linked and endogenous Gi-proteins. Comparisons of their contributions to GTPase activity and signal transduction and analysis of receptor G-protein activation stoichiometry. J. Biol. Chem. 273, 10367–10375 (1998).
  Article CAS PubMed Google Scholar
• Wade, S. M. et al. Gi activator region of α2A-adrenergic receptors: distinct basic residues mediate Gi versus Gs activation. Mol. Pharmacol. 56, 1005–1013 (1999).
  Article CAS PubMed Google Scholar
• McLatchie, L. M. et al. RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature 393, 333–339 (1998).This paper is one of the first to describe accessory proteins that completely change receptor phenotypes by physical association.
  Article CAS PubMed Google Scholar
• Foord, S. M. & Marshall, F. H. RAMPS: Accessory proteins for seven transmembrane domain receptors. Trends Pharmacol. Sci. 20, 184–187 (1999).
  Article CAS PubMed Google Scholar
• Armour, S. L., Foord, S., Kenakin, T. & Chen, W.-J. Pharmacological characterization of receptor-activity-modifying proteins (RAMPs) and the human calcitonin receptor. J. Pharmacol. Toxicol. Methods 42, 217–224 (1999).
  Article CAS PubMed Google Scholar
• Sato, M. et al. Factors determining specificity of signal transduction by G-protein coupled receptors. J. Biol. Chem. 270, 15269–15276 (1993).
  Article Google Scholar
• Nanoff, C., Mitteraurer, T., Roka, F., Hohenegger, M. & Friessmuth, M. Species differences in A1 adenosine/G-protein coupling: identification of a membrane protein that stabilizes the association of the receptor/G-protein complex. Mol. Pharmacol. 48, 806–817 (1995).
  CAS PubMed Google Scholar
• Hall, R. A. et al. The β2-adrenergic receptor interacts with the Na+/H+-exchanger regulatory factor to control Na+/H+ exchange. Nature 392, 626–630 (1998).
  Article CAS PubMed Google Scholar
• Ullmer, C., Schmuck, K., Figge, A. & Lubbert, H. Cloning and characterization of MUPP1, a novel PDZ domain protein. FEBS Lett. 424, 63–68 (1998).
  Article CAS PubMed Google Scholar
• Hall, R. A., Premont, R. T. & Lefkowitz, R. J. Heptahelical receptor signaling: beyond the G-protein paradigm. J. Cell Biol. 145, 927–932 (1999).
  Article CAS PubMed Central PubMed Google Scholar
• Abdalla, S., Lother, H. & Quitterer, U. AT1-receptor heterodimers show enhanced G-protein activation and altered receptor sequestration. Nature 407, 94–98 (2000).
  Article CAS PubMed Google Scholar
• Rocheville, M. et al. Receptors for dopamine and somatostatin: formation of hetero-oligomers with enhanced functional activity. Science 288, 154–157 (2000).
  Article CAS PubMed Google Scholar
• Smith, M. W. et al. Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC), ALIVE Study. Science 277, 959–965 (1997).
  Article CAS PubMed Google Scholar
• Costa, T. & Herz, A. Antagonists with negative intrinsic activity at δ-opioid receptors coupled to GTP-binding proteins. Proc. Natl Acad. Sci. USA 86, 7321–7325 (1989).The first clear demonstration of constitutive activity for GPCRs that was not due to residual agonist in the medium. This work necessitated the complete revision of the ternary complex model.
  Article CAS PubMed PubMed Central Google Scholar
• Katz, B. & Thesleff, S. A study of the 'desensitization' produced by acetylcholine at the motor end plate. J. Physiol. (Lond.) 138, 63–80 (1957).
  Article CAS Google Scholar
• Del Castillo, J. & Katz, B. Interaction at end-plate receptors between different choline derivatives. Proc. R. Soc. London B 146, 369–381 (1957).
  Article CAS Google Scholar
• Colquhoun, D. Imprecision in presentation of binding studies. Trends Pharmacol. Sci. 6, 197 (1985).
• Karlin, A. On the application of 'a plausible model' of allosteric proteins to the receptor for acetylcholine. J. Theoret. Biol. 16, 306–320 (1967).
  Article CAS Google Scholar
• Thron, C. D. On the analysis of pharmacological experiments in terms of an allosteric receptor model. Mol. Pharmacol. 9, 1–9 (1973).
  Article CAS PubMed Google Scholar
• Leff, P. The two-state model of receptor activation. Trends Pharmacol. Sci. 16, 89–97 (1995).
  Article CAS PubMed Google Scholar
• Gether, U., Lin, S. & Kobilka, B. K. Fluorescent labeling of purified β2-adrenergic receptor: evidence for ligand specific conformational changes. J. Biol. Chem. 270, 28268–28275 (1995).
  Article CAS PubMed Google Scholar
• Bohm, S. K., Grady, E. F. & Bunnett, N. W. Regulatory mechanisms that modulate signaling by G-protein-coupled receptors. Biochem. J. 322, 1–18 (1997).
  Article CAS PubMed Central PubMed Google Scholar
• Koenig, J. A. & Edwardson, J. M. Endocytosis and recycling of G-protein-coupled receptors. Trends Pharmacol. Sci. 18, 276–287 (1997).
  Article CAS PubMed Google Scholar
• Riccobene, T. A., Omann, G. M. & Linderman, J. J. Modeling activation and desensitization of G-protein coupled receptors provides insight into ligand efficacy. J. Theor. Biol. 200, 207–222 (1999).
  Article CAS PubMed Google Scholar
• Remmers, A. E., Clark, M. J., Ynag, X. & Medzihradsky, F. δ-opioid receptor down-regulation is independent of functional G-protein yet is dependent on agonist efficacy. J. Pharmacol. Exp. Ther. 287, 625–632 (1998).
  CAS PubMed Google Scholar
• Zaki, P. A. et al. Agonist-, antagonist- and inverse agonist-regulated trafficking of the δ-opioid receptor correlates with, but does not require, G-protein activation. J. Pharmacol. Exp. Ther. 298, 1015–1020 (2001).
  CAS PubMed Google Scholar
• Roettger, B. F. et al. Antagonist-stimulated internalization of the G protein-coupled cholecystokinin receptor. Mol. Pharmacol. 51, 357–366 (1997).
  CAS PubMed Google Scholar
• Alkhatib, G. et al. A RANTES, MIP-1α, MIP-1β receptor as a fusion co-factor for macrophage-tropic HIV-1. Science 272, 1955–1958 (1996).
  Article CAS PubMed Google Scholar
• Cocchi, F., DeVico, A. L., Garzino-Demo, A., Cara, R. C. & Lusso, P. The V3 domain of the HIV gp120 envelope glycoprotein is critical for chemokine-mediated blockade of infection. Nature Med. 2, 1244–1247 (1996).
  Article CAS PubMed Google Scholar
• Simmons, G. et al. Potential inhibition of HIV-1 infectivity in macrophages and lymphocytes by a novel CCR5 antagonist. Science 276, 276–279 (1997).
  Article CAS PubMed Google Scholar
• Amara, A. et al. HIV co-receptor down-regulation as an antiviral principle: SDF-1 α-dependent internalization of the chemokine receptor CXCR4 contributes to inhibition of HIV replication. J. Exp. Med. 186, 139–146 (1997).
  Article CAS PubMed Central PubMed Google Scholar
• Mack, M. et al. Aminooxypentane–RANTES induces CCR5 internalization but inhibits recycling: a novel inhibitory mechanism of HIV infectivity. J. Exp. Med. 187, 1215–2438 (1998).
  Article CAS PubMed Central PubMed Google Scholar
• Rodriguez-Frade, J. M. et al. Similarities and differences in RANTES- and (AOP)-RANTES-triggered signals: implications for chemotaxis. J. Cell Biol. 144, 755–765 (1999).
  Article CAS PubMed Central PubMed Google Scholar
• Thomas, W. G., Quian, H., Chang, C.-S. & Karnik, S. Agonist-induced phosphorylation of the angiotensin II (AT1A) receptor requires generation of a conformation that is distinct from the inositol phosphate-signaling state. J. Biol. Chem. 275, 2893–2900 (2000).
  Article CAS PubMed Google Scholar
• Chakrabarti, S., Law, P. Y. & Loh, H. H. Distinct differences between morphine- and [δ-Ala2,_N_-MePhe4,Gly-ol5]enkephalin-μ-opioid complexes demonstrated by cyclic independent protein kinase phosphorylation. J. Neurochem. 71, 231–239 (1998).
  Article CAS PubMed Google Scholar
• Yu, Y. et al. μ-Opioid receptor phosphorylation, desensitization, and ligand efficacy. J. Biol. Chem. 272, 28869–28874 (1997).
  Article CAS PubMed Google Scholar
• Blake, A. D., Bot, G., Freeman, J. C. & Reisine, T. Differential opioid agonist regulation of the mouse μ-opioid receptor. J. Biol. Chem. 272, 782–790 (1997).
  Article CAS PubMed Google Scholar
• Keith, D. E. et al. Morphine activates opioid receptors without causing their rapid internalization. J. Biol. Chem. 271, 19021–19249 (1996).
  Article CAS PubMed Google Scholar
• Morisset, S. et al. High constitutive activity of native H3 receptors regulates histamine neurons in brain. Nature 408, 860–864 (2000).
  Article CAS PubMed Google Scholar
• Kenakin, T. P. Drug efficacy at G-protein coupled receptors. FASEB J. 15, 598–611 (2001).
  Article CAS PubMed Google Scholar
• Morris, B. J. & Millan, M. J. Inability of an opioid antagonist lacking negative intrinsic activity to induce opioid receptor up-regulation in vivo. Br. J. Pharmacol. 102, 883–886 (1991).
  Article CAS PubMed Central PubMed Google Scholar
• Smit, M. J. et al. Inverse agonism of histamine H2 antagonists accounts for up-regulation of spontaneously active histamine H2 receptors. Proc. Natl Acad. Sci. USA 93, 6802–6807 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• MacEwan, D. J. & Milligan, G. Inverse agonist-induced up-regulation of the human β2-adrenoceptor in transfected neuroblastoma X glioma hybrid cells. Mol. Pharmacol. 50, 1479–1486 (1996).
  CAS PubMed Google Scholar
• Milligan, G. & Bond, R. A. Inverse agonism and the regulation of receptor number. Trends Pharmacol. Sci. 18, 468–474 (1997).
  Article CAS PubMed Google Scholar
• Berg, K. A., Stout, B. D., Cropper, J. D., Maayani, S. & Clarke, W. P. Novel actions of inverse agonists on 5-HT2C receptor systems. Mol. Pharmacol. 55, 863–872 (1999).
  CAS PubMed Google Scholar
• Nagaraja, S., Iyer, S., Liu, X., Eichberg, J. & Bond, R. A. Treatment with inverse agonists enhances baseline atrial contractility in transgenic mice with chronic β2-adrenoceptor activation. Br. J. Pharmacol. 127, 1099–1104 (1999).
  Article CAS PubMed Central PubMed Google Scholar
• Chen, G. et al. Use of constitutive G protein-coupled receptor activity for drug discovery. Mol. Pharmacol. 57, 125–134 (1999).
  Google Scholar
• Chen, G. et al. Constitutive receptor systems for drug discovery. J. Pharmacol. Toxicol. Methods 42, 199–206 (1999).
  Article CAS PubMed Google Scholar
• Jayawickreme, C. K., Graminski, G. F., Quillan, J. M. & Lerner, M. R. Creation and functional screening of a multi-use peptide library. Proc. Natl Acad. Sci. USA 91, 1614–1618 (1994).
  Article CAS PubMed PubMed Central Google Scholar
• Jayawickreme, C. K., Graminski, G. F., Quillan, J. M. & Lerner, M. R. Discovery and structure–function analysis of α-melanocyte-stimulating hormone antagonists. J. Biol. Chem. 269, 29846–29854 (1994).
  CAS PubMed Google Scholar
• Lerner, M. R. Tools for investigating functional interactions between ligands and G-protein-coupled receptors. Trends Neurosci. 17, 142–146 (1994).
  Article CAS PubMed Google Scholar
• Chen, W.-J. et al. Recombinant human CXC-chemokine receptor-4 in melanophores are linked to Gi protein: seven transmembrane coreceptors for human immunodeficiency virus entry into cells. Mol. Pharmacol. 53, 177–181 (1998).
  Article CAS PubMed Google Scholar
• Kenakin, T. P. in Biomedical Applications of Computer Modeling (ed. Christopoulos, A.) 1–20 (CRC Press, Florida, 2000).
  Book Google Scholar
• Samama, P., Cotecchia, S., Costa, T. & Lefkowitz, R. J. A mutation-induced activated state of the β2-adrenergic receptor: extending the ternary complex model. J. Biol. Chem. 268, 4625–4636 (1993).This paper discusses the intrinsic property of receptors to form an active state in the absence of ligand, and so is the first to introduce the extended ternary complex model for GPCRs.
  CAS PubMed Google Scholar
• Weiss, J. M., Morgan, P. H., Lutz, M. W. & Kenakin, T. P. The cubic ternary complex receptor-occupancy model. I. Model description. J. Theor. Biol. 178, 151–167 (1996).
  Article CAS Google Scholar
• Weiss, J. M., Morgan, P. H., Lutz, M. W. & Kenakin, T. P. The cubic ternary complex receptor-occupancy model. II. Understanding apparent affinity. J. Theor. Biol. 178, 169–182 (1996).
  Article CAS Google Scholar
• Weiss, J. M., Morgan, P. H., Lutz, M. W. & Kenakin, T. P. The cubic ternary complex receptor-occupancy model. III. Resurrecting efficacy. J. Theor. Biol. 181, 381–397 (1996).References 90–92 describe a more thermodynamically complete (but more complex) version of the extended ternary complex model. It allows non-activated receptors to interact with G proteins to produce non-signalling species.
  Article CAS PubMed Google Scholar
• Freire, E. Can allosteric regulation be predicted from structure? Proc. Natl Acad. Sci. USA 97, 11680–11682 (2000).
  Article CAS PubMed PubMed Central Google Scholar