Inverse agonism at heptahelical receptors: Concept, experimental approach and therapeutic potential

Fundamental and Clinical Pharmacology

Volumn 14, Issue 2, 2000, Pages 73-87

  Daeffler, Laurent ^a   Landry, Yves ^a  

^a INSERM   (France)

Author keywords

Constitutively active receptor; G protein; Inverse agonist; Ternary complex model; Two state model

Indexed keywords

GUANINE NUCLEOTIDE BINDING PROTEIN; GUANINE NUCLEOTIDE BINDING PROTEIN ANTAGONIST; GUANOSINE TRIPHOSPHATASE INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL CELL; BINDING COMPETITION; BINDING KINETICS; CONTROLLED STUDY; DRUG RECEPTOR BINDING; GENE OVEREXPRESSION; INHIBITION KINETICS; LIGAND BINDING; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN QUATERNARY STRUCTURE; RAT; RECEPTOR AFFINITY; RECEPTOR DOWN REGULATION; RECEPTOR OCCUPANCY; RECEPTOR UPREGULATION; REVIEW;

EID: 0034032765     PISSN: 07673981     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1472-8206.2000.tb00395.x     Document Type: Review

References (121)

1. [1] Braestrup C., Schmiechen R., Neef G., Nielsen M., Petersen E.N., Interaction of convulsive ligands with benzodiazepine receptors, Science 216 (1982) 1241-1243.
2. [2] Schütz W., Freissmuth M., Reverse intrinsic activity of agonists on G protein-coupled receptors, Trends Pharmacol. Sci. 13 (1992) 376-380.
3. [3] Gilman A.G., G proteins: transducers of receptor-generated signals, Ann. Rev. Biochem. 56 (1987) 615-649.
4. [4] Costa T., Hertz A., Antagonists with negative intrinsic activity at δ opioid receptors coupled to GTP-binding proteins, Proc. Natl. Acad. Sci. USA 86 (1989) 7321-7325.
5. [5] Hill A.W., The possible effects of the aggregation of the molecules of haemoglobin on its dissociation curves, J. Physiol. (London) 39 (1910) 4-7.
6. [6] Clark A.J., The mode of action of drugs on cells, Edward Arnold, London, 1933.
7. [7] Ariens E.J., Affinity and intrinsic activity in the theory of competitive inhibition, 1, problems and theory, Arch. Int. Pharmacodyn. 99 (1954) 32-49.
8. [8] Stephenson R.P., A modification of receptor theory, Br. J. Pharmacol. 11 (1956) 379-393.
9. [9] Furchgott R.F., The use of b-halohalkylamines in the differentiation of receptors and in the determination of dissociation constants of receptor-agonist complexes, Adv. Drug Res. 3 (1966) 21-55.
10. [10] Colquhoun D., Binding, gating, affinity and efficacy: the interpretation of structure-activity relationships for agonists and the effects of mutating receptors, Br. J. Pharmacol. 125 (1998) 924-947.
11. [11] Wyman J.J., Allen D.W., The problem of the haem interaction in haemoglobin and the basis of the Bohr effect, J. Polymer Sci. 7 (1951) 499-518.
12. [12] Del Castillo J., Katz B., Interaction at end-plate receptors between different choline derivatives, Proc. Roy. Soc. Lond. B. 146 (1957) 369-381.
13. [13] Monod J., Wyman J., Changeux J.P., On the nature of allosteric transition: a plausible model, J. Mol. Biol. 12 (1965) 306-329.
14. [14] Rodbell M., Krans H.M.J., Pohl S.L., Birnbaumer L., The glucagon-sensitive adenyl cyclase system in plasma membranes of rat liver. IV. Effect of guanyl nucleotides on binding of 1251-glucagon, J. Biol. Chem. 246 (1971) 1872-1876.
15. [15] Rodbell M., Birnbaumer L., Pohl S.L., Krans H.M.J., The glucagon-sensitive adenyl cyclase system in plasma membranes of rat liver. V. An obligatory role of guanyl nucleotides in glucagon action, J. Biol. Chem. 246 (1971) 1877-1882.
16. [16] Maguire M.E., Van Arsdale P.M., Gilman A.G., An agonist-specific effect of guanine nucleotides on binding to the beta adrenergic receptor, Mol. Pharmacol. 12 (1976) 335-339.
17. [17] Lefkovitz R.J., Mullikin D., Caron M.G., Regulation of b-adrenergic receptors by guanyl-5′-yl imidodiphosphate and other purine nucleotides, J. Biol. Chem. 251 (1976) 4686-4692.
18. [18] Birdsall N.J.M., Burgen A.S.V., Hulme E.C., The binding of agonist to brain muscarinic receptors, Mol. Pharmacol. 14 (1978) 723-736.
19. [19] Hulme E.C., Birdsall N.J.M., Burgen A.S.V., Metha P., The binding of antagonists to brain muscarinic receptors, Mol. Pharmacol. 14 (1978) 737-750.
20. [20] Berrie C.P., Birdsall N.J.M., Burgen A.S.V., Hulme E.C., Guanine nucleotides modulate muscarinic receptor binding in the heart, Biochem. Biophys. Res. Comm. 87 (1979) 1000-1005.
21. [21] De Lean A., Stadel J.M., Lefkowitz R.J., A ternary complex explains the agonist-specific binding properties of the adenylate cyclase-coupled β-adrenergic receptor, J. Biol. Chem. 255 (1980) 7108-7117.
22. [22] Burgisser E., De Lean A., Lefkowitz R.J., Reciprocal modulation of agonist and antagonist binding to muscarinic cholinergic receptor by guanine nucleotide, Proc. Natl. Acad. Sci. USA 79 (1982) 1732-1736.
23. [23] Wreggett K.A., De Lean A., The ternary complex model. Its properties and application to ligand interactions with the D2-dopamine receptor of the anterior pituitary gland, Mol. Pharmacol. 26 (1984) 214-227.
24. [24] Kenakin T., Receptor theory, in: Enna S.J., Williams M. et al. (Eds.), Current protocols in pharmacology, John Wiley & Sons Inc, NY, 1998, p. 1.2.1.
25. 2-adrenergic receptor: extending the ternary complex model, J. Biol. Chem. 268 (1993) 4625-4636.
26. [26] Lefkowitz R.J., Cotecchia S., Samama P., Costa T., Constitutive activity of receptors coupled to guanine nucleotide regulatory proteins, Trends Pharmacol. Sci. 14 (1993) 303-307.
27. [27] 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 (1996) 151-167.
28. [28] 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 (1996) 169-182.
29. [29] 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 (1996) 381-397.
30. [30] Milligan G., Mechanisms of multifunctional signalling by G protein-linked receptors, Trends Pharmacol. Sci. 14 (1993) 239-244.
31. [31] Kenakin T., Agonist-receptor efficacy I: mechanisms of efficacy and receptor promiscuity, Trends Pharmacol. Sci. 16 (1995) 188-192.
32. [32] Leff P., Scaramellini C., Law C., McKechnie K., A three-state receptor model of agonist action, Trends Pharmacol. Sci. 18 (1997) 355-362.
33. [33] Kenakin T., Agonist-receptor efficacy II: agonist trafficking of receptor signals, Trends Pharmacol. Sci. 16 (1995) 232-238.
34. [34] Kenakin T., Agonist-specific receptor conformations, Trends Pharmacol. Sci. 18 (1997) 416-417.
35. [35] Kenakin T., Protein agonists, key to receptor active states?, Ann. NY Acad. Sci. 812 (1997) 116-125.
36. [36] Onaran H.O., Costa T., Agonist efficacy and allosteric models of receptor action, Ann. NY Acad. Sci. 812 (1997) 98-115.
37. [37] Hebert T.E., Bouvier M., Structural and functional aspects of G protein-coupled receptor oligomerization, Biochem. Cell Biol. 76 (1998) 1-11.
38. [38] Onaran H.O., Gürdal H., Ligand efficacy and affinity in an interacting 7TM receptor model, Trends Pharmacol. Sci. 20 (1999) 274-278.
39. [39] Bauer P.H., Müller S., Puzicha M., Pippig S., Obermaier B., Helmreich E.J.M., Lohse M.J., Phosducin is a protein kinase A-regulated G-protein regulator, Nature 358 (1993) 73-76.
40. [40] Gouldson P.R., Snell C.R., Bywater R.P., Higgs C., Reynolds C.A., Domain swapping in the G-protein coupled receptor dimers, Protein Eng. 11 (1998) 1181-1183.
41. [41] Berman D.M., Gilman A.G., Mammalian RGS proteins: barbarians at the gate, J. Biol. Chem. 273 (1998) 1269-1272.
42. [42] De Vries L., Mousli M., Wurmser A., Farquarhar M.G., GAIP, a protein that specifically interacts with the trimeric G protein G alpha i3, is a member of a protein family with a highly conserved core domain, Proc. Natl. Acad. Sci USA 92 (1995) 11916-11920.
43. [43] Danner S., Lohse M.J., Phosducin is a ubiquitous G-protein regulator, Proc. Natl. Acad. Sci. USA 93 (1996) 10145-10150.
44. [44] Bunemann M., Hosey M.M., G-protein coupled receptor kinases as modulators of G-protein signalling, J. Physiol. (London) 517 (1999) 5-53.
45. + exchange, Nature 392 (1998) 626-630.
46. [46] Bockaert J., Audigier Y., Homburger V., Rouot B., Les proteines G de transduction, in: Landry Y., Gies J.P. (Eds.), Pharmacologie Moléculaire. Mécanisme d'action des médiateurs et des médicaments, Arnette, Paris, 1993, p. 137.
47. [47] Cassel D., Selinger Z., Catecholamine-stimulated GTPase activity in turkey erythrocyte membranes, Biochim. Biophys. Acta 452 (1976) 538-551.
48. [48] Cassel D., Selinger Z., Mechanism of adenylate cyclase activation by cholera toxin: inhibition of GTP hydrolysis at the regulatory site, Proc. Natl. Acad. Sci. USA 74 (1977) 3307-3311.
49. [49] Abood M.E., Hurley J.B., Pappone M.C., Bourne H.R., Stryer L., Functional homology between signal coupling proteins. Cholera toxin inactivates the GTPase activity of transducin, J. Biol. Chem. 257 (1982) 10540-10543.
50. [50] Kahn R.A., Gilman A.G., ADP-ribosylation of Gs promotes the dissociation of its alpha and beta subunits, J. Biol. Chem. 259 (1984) 6235-6240.
51. [51] Daeffler L., Chahdi A., Gies J.P., Landry Y., Inhibition of GTPase activity of Gi proteins and decreased agonist affinity at M2 muscarinic acetylcholine receptors by spermine and methoctramine, Br. J. Pharmacol. 127 (1999) 1021-1029.
52. [52] Ui M., Katada T., Muragama T., Kurose H., Yajimaz M., Tamura M., Nakamura T., Nogimori K., Islet-activating protein, pertussis toxin: A specific uncoupler of receptor-mediated inhibition of adenylate cyclase, Adv. Cycl. Nucl. Prot. Phos. Res. 17 (1984) 141-151.
53. [53] Chahdi A., Daeffler L., Gies J.P., Landry Y., Drugs interacting with G proteins α subunits: selectivity and perspectives, Fundam. Clin. Pharmacol. 12 (1998) 121-132.
54. [54] Freissmuth M., Waldhoer M., Bofill-Cardona E., Nanoff C., G protein antagonists, Trends Pharmacol. Sci. 20 (1999) 237-245.
55. [55] Mukai H., Munekata E., Higashijima T., G protein antagonists, a novel hydrophobic peptide competes with receptor for G protein binding, J. Biol. Chem. 267 (1992) 16237-16243.
56. [56] Daeffler L., Schimdlin F., Gies J.P., Landry Y., Inverse agonist activity of pirenzepine for M2 muscarinic acetylcholine receptors, Br. J. Pharmacol. 126 (1999) 1246-1252.
57. [57] Hohenegger M., Waldhoer M., Beindl W., Boing B., Kreimeyer A., Nickel P., Nanoff C., Freissmuth M., Gs alpha-selective G protein antagonists , Proc. Natl. Acad. Sci. USA 95 (1998) 346-351.
58. [58] Mousli M., Bueb J.L., Bronner C., Rouot B., Landry Y., G protein activation: a receptor-independent mode of action for cationic amphophilic peptides and venom peptides, Trends Pharmacol. Sci. 11 (1990) 358-362.
59. [59] Klinker J.F., Hageluken A., Grunbaum L., Seifert R., Direct and indirect receptor-independent G-protein activation by cationic-amphiphilic substances. Studies with mast cells, HL-60 human leukemic cells and purified G-proteins, Exp. Dermatol. 4 (1995) 231-239.
60. [60] Higashijima T., Uzu S., Nakajima T., Ross E.M., Mastoparan, a peptide toxin from wasp venom, mimics receptors by activating GTP-binding regulatory proteins (G proteins), J. Biol. Chem. 263 (1988) 6491-6494.
61. [61] Mousli M., Bronner C., Bueb J.L., Tschirhart E., Gies J.P., Landry Y., Activation of rat peritoneal mast cells by substance P and mastoparan, J. Pharmacol. Exp. Ther. 250 (1989) 329-335.
62. [62] Aridor M., Traub L., Sagi-Eisenberg R., Exocytosis in mast cells by basic secretagogues, evidence for direct activation of GTP-binding proteins, J. Cell. Biol. 111 (1990) 909-917.
63. [63] Mousli M., Bronner C., Landry Y., Bockaert J., Rouot B., Direct activation of GTP-binding regulatory protein (G proteins) by substance P and compound 48/80, FEBS Lett. 259 (1990) 260-262.
64. [64] Gies J.P., Approche par liaison spécifique de la caractérisation des ligands et des récepteurs, in: Landry Y., Gies J.P. (Eds.), Pharmacologie Moléculaire. Mécanisme d'action des médiateurs et des médicaments, Arnette, Paris, 1993, p. 31.
65. [65] McKinney M., Practical aspects of radioligand binding, in: Enna S.J., Williams M. et al. (Eds.), Current protocols in pharmacology, John Wiley & Sons Inc, NY, 1998, p. 1.3.1.
66. 50) of an enzymatic reaction, Biochem. Pharmacol. 22 (1973) 3099-3103.
67. [67] Costa T., Ogino Y., Munson P.J., Onara H.O., Rodbard D., Drug efficacy at guanine nucleotide-binding regulatory protein-linked receptors: thermodynamic interpretation of negative antagonism and the receptor activity in the absence of ligand, Mol. Pharmacol. 41 (1992) 549-560.
68. [68] Van Gelderen J.G., Daeffler L., Scherrer D., Mousli M., Landry Y., Gies J.P., Mé-muscarinic receptors: how does ligand affinity relate to intrinsic activity?, J. Recept. Signal Transduct. Res. 16 (1996) 135-148.
69. [69] Neilan C.L., Akil H., Woods J.H., Traynor J.R., Constitutive activity of the delta-opioid receptor expressed in C6 glioma cells: identification of non-peptide delta-inverse agonists, Br. J. Pharmacol. 128 (1999) 556-562.
70. [70] Hosohata K., Burkey T.H., Alfaro-Lopez J., Hruby V.J., Roeske W.R., Yamamura H.I., (2S, 3R)TMT-L-Tic-OH is a potent inverse agonist at the human delta-opioid receptor, Eur. J. Pharmacol. 380 (1999) R9-R10.
71. [71] Chidiac P., Hebert T.E., Valiquette M., Dennis M., Bouvier M., Inverse agonist activity of α-adrenergic antagonists, Mol. Pharmacol. 45 (1994) 490-499.
72. [72] Garcia-Sainz J.A., Torres-Padilla M.E., Modulation of basal intracellular calcium by inverse agonists and phorbol myristate acetate in rat-1 fibroblasts stably expressing alpha1d-adrenoceptors, FEBS Lett. 443 (1999) 277-281.
73. [73] Cotecchia S., Lattion A.L., Diviani D., Cavalli A., Signalling and regulation of the alpha 1B-adrenergic receptor, Biochem. Soc. Trans. 23 (1995) 121-125.
74. [74] Rossier O., Abuin L., Fanelli F., Leonardi A., Cotecchia S., Inverse agonism and neutral antagonism at alpha (1a)- and alpha (1b)-adrenergic receptor subtypes, Mol. Pharmacol. 56 (1999) 858-866.
75. [75] Shi A.G., Deth R.C., Precoupling of alpha-2B adrenergic receptors and G-proteins in transfected PC-12 cell membranes: influence of pertussis toxin and a lysine-directed cross-linker, J. Pharmacol. Exp. Ther. 271 (1994) 1520-1527.
76. [76] Smit M.J., Leurs R., Alewijnse A.E., Blauw J., Van Nieuw Amerongen G.P., Van De Vrede Y., Roovers E., Timmerman H., Inverse agonism of histamine H2 antagonist accounts for upregulation of spontaneously active histamine H2 receptors, Proc. Natl. Acad. Sci. USA 93 (1996) 6802-6807.
77. [77] Cai G., Gurdal H., Smith C., Wang H.Y., Friedman E., Inverse agonist properties of dopaminergic antagonists at the D(1A) dopamine receptor: uncoupling of the D(1A) dopamine receptor from G(s) protein, Mol. Pharmacol 56 (1999) 989-996.
78. [78] Nilsson C.L., Ekman A., Hellstrand M., Eriksson E., Inverse agonism at dopamine D2 receptors. Haloperidol-induced prolactin release from GH4C1 cells transfected with the human D2 receptor is antagonized by ( - )-n-propylnorapomorphine, raclopride, and phenoxybenzamine, Neuropsychopharmacology 15 (1996) 53-61.
79. [79] Malmberg A., Mohell N., Backlund Hook B., Johansson A.M., Hacksell U., Nordvall G., Interactions of ligands with active and inactive conformations of the dopamine D2 receptor, Eur. J. Pharmacol. 346 (1998) 299-307.
80. [80] Strange P.G., Agonism and inverse agonism at dopamine D2-like receptors, Clin. Exp. Pharmacol. Physiol. 26 suppl. (1999) S3-S9.
81. [81] Newman-Tancredi A., Conte C., Chaput C., Speeding M., Millan M.J., Inhibition of the constitutive activity of human 5-HT1A receptors by the inverse agonist, spiperone but not the neutral antagonist, WAY 100,635, Br. J. Pharmacol. 120 (1997) 737-739.
82. [82] Barker E.L., Westphal R.S., Schmidt D., Sanders-Bush E., Constitutively active 5-hydroxytryptamine 2C receptors reveal novel inverse agonist activity of receptor ligands, J. Biol. Chem. 269 (1994) 11687-11690.
83. [83] Labrecque J., Fargin A., Bouvier M., Chidiac P., Dennis M., Serotonergic antagonists differentially inhibit spontaneous activity and decrease ligand binding capacity of the rat 5-hydroxytryptamine type 2C receptor in Sf9 cells, Mol. Pharmacol. 48 (1995) 150-159.
84. [84] Pauwels P.J., Wurch T., Palmier C., Colpaert F.C., Pharmacological analysis of G-protein activation mediated by guinea-pig recombinant 5-HT1B receptors in C6-glial cells: similarities with the human 5-HT1B receptor, Br. J. Pharmacol. 123 (1998) 51-62.
85. [85] Pauwels P.J., Gouble A., Wurch T., Activation of constitutive 5-hydroxytryptamine 1B receptor by a series of mutations in the BBXXB motif: positioning of the third intracellular loop distal junction and its Go alpha protein interactions, Biochem. J. 343 (1999) 435-442.
86. [86] Blondel O., Gastineau M., Langlois M., Fischmeister R., The 5-HT4 receptor antagonist ML10375 inhibits the constitutive activity of human 5-HT4(c) receptor, Br. J. Pharmacol. 125 (1998) 595-597.
87. [87] Thomas D.R., Gittins S.A., Collin L.L., Middlemiss D.N., Riley G., Hagan J., Gloger I., Ellis C.E., Forbes I.T., Brown A.M., Functional characterisation of the human cloned 5-HT7 receptor (long form); antagonist profile of SB-258719, Br. J. Pharmacol. 124 (1998) 1300-1306.
88. [88] Middlemiss D.N., Gothert M., Schlicker E., Scott C.M., Selkirk J.V., Watson J., Gaster L.M., Wyman P., Riley G., Price G.W., SB-236057, a selective 5-HT1B receptor inverse agonist blocks the 5-HT human terminal autoreceptor, Eur. J. Pharmacol. 375 (1999) 359-365.
89. [89] Roka F., Brydon L., Waldhoer M., Strosberg A.D., Freissmuth M., Jockers R., Nanoff C., Tight association of the human Mel(1a)-melatonin receptor and G(i): precoupling and constitutive activity, Mol. Pharmacol. 56 (1999) 1014-1024.
90. [90] MacLennan S.J., Reynen P.H., Kwan J., Bonhaus D.W., Evidence for inverse agonism of SR141716A at human recombinant cannabinoid CB1 and CB2 receptors, Br. J. Pharmacol. 124 (1998) 619-622.
91. [91] Portier M., Rinaldi-Carmona M., Pecceu F., Combes T., Poinot-Chazel C., Calandra B., Barth F., le Fur G., Casellas P.J., SR 144528, an antagonist for the peripheral cannabinoid receptor that behaves as an inverse agonist, J. Pharmacol. Exp. Ther. 288 (1999) 582-589.
92. [92] Ross R.A., Gibson T.M., Stevenson L.A., Saha B., Crocker P., Razdan R.K., Pertwee R.G., Structural determinants of the partial agonist-inverse agonist properties of 6′-azidohex-2′-yne-Delta8-tetrahydrocannabinol at cannabinoid receptors, Br. J. Pharmacol. 128 (1999) 735-743.
93. [93] Shryock J.C., Ozeck M.J., Belardinelli L., Inverse agonists and neutral antagonists of recombinant human A1 adenosine receptors stably expressed in Chinese hamster ovary cells, Mol. Pharmacol. 53 (1998) 886-893.
94. [94] Morin D., Cotte N., Balestre M.N., Mouillac B., Manning M., Breton C., Barberis C., The D136A mutation of the V2 vasopressin receptor induces a constitutive activity which permits discrimination between antagonists with partial agonist and inverse agonist activities, FEBS Lett. 441 (1998) 470-475.
95. [95] Fathy D.B., Leeb T., Mathis S.A., Leeb-Lundberg L.M., Spontaneous human B2 bradykinin receptor activity determines the action of partial agonists as agonists or inverse agonists. Effect of basal desensitization, J. Biol. Chem. 274 (1999) 29603-29606.
96. [96] Millan M.J., Gobert A., Audinot V., Dekeyne A., Newman-Tancredi A., Inverse agonists and serotonergic transmission: from recombinant, human serotonin (5-HT)1B receptors to G-protein coupling and function in corticolimbic structures in vivo, Neuropsychopharmacology 21 suppl. (1999) 61S-67S.
97. + currents in frog and rat cardiac cells, J. Physiol. (London) 461 (1993) 743-765.
98. [98] Spiegel A.M., Defects in protein-coupled signal transduction in human disease, Annu. Rev. Physiol. 58 (1996) 143-170.
99. [99] Pauwels P.J., Wurch T., Review: amino acid domains involved in constitutive activation of G-protein-coupled receptors, Mol. Neurobiol. 17 (1998) 109-135.
100. [100] Gardella T.J., Luck M.D., Jensen G.S., Schipani E., Potts J.T. Jr., Juppner H., Inverse agonism of amino-terminally truncated parathyroid hormone (PTH) and PTH-related peptide (PTHrP) analogs revealed with constitutively active mutant PTH/ PTHrP receptors, Endocrinology 137 (1996) 3936-3941.
101. [101] Allen L.F., Lefkowitz R.J., Caron M.G., Cotecchia S., G-protein-coupled receptor genes as protooncogenes: constitutively activating mutation of the alpha1B-adrenergic receptor enhances mitogenesis and tumorigenicity, Proc. Natl. Acad. Sci. USA 88 (1991) 11354-11358.
102. [102] Westphal R.S., Sanders-Bush E., Differences in agonist-independent and -dependent 5-hydroxytryptamine 2C receptor-mediated cell division, Mol. Pharmacol. 49 (1996) 474-480.
103. [103] Arvanitakis L., Geras-Raaka E., Varma A., Gershengorn M.C., Cesarman E., Human herpesvirus KSHV encodes a constitutively active G-protein-coupled receptor linked to cell proliferation, Nature 385 (1997) 347-350.
104. [104] Bais C., Santomasso B., Coso O., Arvanitakis L., Raaka E.G., Gutkind J.S., Asch A.S., Cesarman E., Gershengorn M.C., Mesri E.A., G-protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus is a viral oncogene and angiogenesis activator, Nature 391 (1998) 86-89.
105. [105] Milano C.A., Allen L.F., Rockman H.A., Dolber P.C., McMinn T.R., Chien K.R., Johnson T.D., Bond R.A., Lefkowitz R.J., Enhanced myocardial function in transgenic mice overexpressing the beta 2-adrenergic receptor, Science 264 (1994) 582-586.
106. [106] Bond R.A., Leff P., Johnson T.D., Milano C.A., Rockman H.A., McMinn T.R., Apparsundaram S., Hyek M.F., Kenakin T.P., Allen L.F., Lefkowitz R..J., Physiological effects of inverse agonists in transgenic mice with myocardial overexpression of the beta 2-adrenoceptor, Nature 374 (1995) 272-276.
107. 2+ cycling to augment contraction in mouse heart, J. Physiol. (London) 521 (1999) 351-361.
108. [108] Varma D.R., Shen H., Deng X.F., Peri K.G., Chemtob S., Mulay S., Inverse agonist activities of beta-adrenoceptor antagonists in rat myocardium, Br. J. Pharmacol. 127 (1999) 895-902.
109. [109] Nagaraja S., Iyer S., Liu X., Eichberg J., Bond R.A., Treatment with inverse agonists enhances baseline atrial contractility in transgenic mice with chronic beta2-adrenoceptor activation, Br. J. Pharmacol. 127 (1999) 1099-1104.
110. [110] Pei G., Samama P., Lohse M., Wang M., Codina J., Lefkowitz R.J., A constitutively active mutant beta 2-adrenergic receptor is constitutively desensitized and phosphorylated, Proc. Natl. Acad. Sci. USA 91 (1994) 2699-2702.
111. [111] Lee T.W., Cotecchia S., Milligan G., Up-regulation of the levels of expression and function of a constitutively active mutant of the hamster alpha1B-adrenoceptor by ligands that act as inverse agonists, Biochem. J. 325 (1997) 733-739.
112. [112] Heinflink M., Nussenzveig D.R., Grimberg H., Lupu-Meiri M., Oron Y., Gershengorn M.C., A constitutively active mutant thyrotropin-releasing hormone receptor is chronically down-regulated in pituitary cells: evidence using chlordiazepoxide as a negative antagonist, Mol. Endocrinol. 9 (1995) 1455-1460.
113. [113] MacEvan D.J., Milligan G., Inverse agonist-induced up-regulation of the human β-2 adrenoceptor in transfected neuroblastoma X glioma hybrid cells, Mol. Pharmacol. 50 (1996) 1479-1486.
114. [114] Milligan G., Bond R.A., Inverse agonism and the regulation of receptor number, Trends Pharmacol. Sci. 18 (1997) 468-474.
115. [115] Krupnick J.G., Benovic J.L., The role of receptor kinases and arrestins in G protein-coupled receptor regulation, Annu. Rev. Pharmacol. Toxicol. 38 (1998) 289-319.
116. [116] Pitcher J.A., Freedman N.J., Lefkowitz R.J., G protein-coupled receptor kinases, Annu. Rev. Biochem. 67 (1998) 653-692.
117. [117] Clark R.B., Knoll B.J., Barber R., Partial agonists and G protein-coupled receptor desensitization, Trends Pharmacol. Sci. 20 (1999) 279-286.
118. [118] Leurs R., Smit M.J., Alewijnse A.E., Timmerman H., Agonist-independent regulation of constitutively active G-protein-coupled receptors, Trends Biochem. Sci. 23 (1998) 418-422.
119. [119] Morris B.J., Millan M.J., Herz A., Antagonist-induced opioid receptor up-regulation. II. Regionally specific modulation of mu, delta and kappa binding sites in rat brain revealed by quantitative autoradiography, J. Pharmacol. Exp. Ther. 247 (1988) 729-736.
120. [120] Cruz S.L., Villarreal J.E., Volkow N.D., Further evidence that naloxone acts as an inverse opiate agonist: implications for drug dependence and withdrawal, Life Sci. 58 (1996) 381-389.
121. [121] Wang Z., Bilsky E.J., Wang D., Porreca F., Sadee W., 3-Isobutyl-1-methylxanthine inhibits basal mu-opioid receptor phosphorylation and reverses acute morphine tolerance and dependence in mice, Eur. J. Pharmacol. 371 (1999) 1-9.