INDEX

(−)-CPCCOEt, 74, 281, 282 A2A, 35, 40, 49, 73, 99, 105, 142, 148, (−)-PHCCC, 74 180, 212, 325, 327, 342, 345, 351, 353, 2,2′-pyridylsatogen tosylate, 74 358, 359, 363, 365, 369–371, 387–389, 3-chlorophenyl carbamate, 67 397, 399, 403–405, 407, 409, 410, 412, 3′,5′-cyclic adenosine monophosphate 415, 417, 437, 438, 440–445, 449,453, (cAMP), 30, 77, 78, 105, 152, 166, color insert fi gures 14.8, 16.1, 16.2

169, 171–173, 180, 193–195, 198, 210, A2B, 415

216–223, 238, 252, 253, 261, 263, 267, A3, 73, 76, 415 269, 281, 292, 293, 295, 301–303, adenylyl cyclase, 91, 168, 173, 193, 195, 309–312, 317, 318, 364, 467, 468, 216–219, 221, 301, 309, 310, 479 481, 483, color insert fi gs. 7.1, 13.5, adrenergic receptors

13.8 α1A, 73, 142, 413

5HT moduline, 74 α1B, 142, 417

6-aryl-8H-indeno[1,2-d]thiazol-2- α2A, 73, 142, 240, 241, 243, 244, 246, 404

ylamines, 76 α2B, 73

6′-guanidinonaltrindole, 100, 150 α2D, 73

77-LH-28–1 (1-[3-(4-butyl-1-piperidinyl) β1, 2, 36, 48, 142, 246, 325, 327, 345, 349, propyl]-3,3-dihydro-2(1H)- 353, 358, 363–365, 368, 369, 371, quinolinone), 75 387–389, 399, 403, 405, 407, 410, 11-cis-retinal, 35, 95, 245, 329–331, 334, 412–415, 437–442, 444, 445, 448, 453, 336–338, 367, 386, 405, 411, 412, 435, color insert fi gs. 14.7, 16.2

436, 441–444, 447, 465, 471–475, 488, β2, 2, 30, 73, 89, 142, 143, 146, 148, 152, 489, color insert fi g. 16.1 165, 229, 233, 242, 269, 317, 325–327, 331, 342, 343, 345, 348, 350, 356–360, AC-260584 (4-[3-(butylpiperidin-1-yl) 362, 365–369, 387–390, 392, 394, propyl]-7-fl uoro-4H-benzo[1,4] 397–401, 403–405, 407–415, 436–445, oxasin-3-one), 75 447–449, 453, color insert fi gs. 13.8, AC-42 (4-n-butyl-1-[4–2(2-methylphenyl)- 14.7, 15.2, 15.3, 15.5, 16.1, 16.2 4-oxo-1-butyl]-piperidine), 74, 75, adrenocorticotropin (ACTH), 479 294 COPYRIGHTEDADX-47273, MATERIAL 74 actin, 100–103, 260, 261 aequorin, 169, 173, 195, 196, 197, 202, activation cooperativity (δ), 42, 65 292, 293, 312 adenomatous polyposis coli (APC), 122 affi nity, 10, 11, 17, 18, 20, 21, 27, 28, 41, adenosine receptors 42, 47, 62–68, 71, 79, 209, 213, 215,

A1, 42, 49, 73, 76, 142, 148, 282, 415 278–285, 295, 304, 489

GPCR Molecular Pharmacology and Drug Targeting: Shifting Paradigms and New Directions, Edited by Annette Gilchrist Copyright © 2010 John Wiley & Sons, Inc.

511

bbindex.inddindex.indd 511511 55/4/2010/4/2010 110:11:200:11:20 AAMM 512 INDEX

agmatine, 73 aspirin, 74 agonist association/dissociation rates, 28, 70, 211, allosteric, 10, 37, 41, 42, 65, 75–77, 179, 215, 280 197, 267, 277–279, 280–282, 284, asymmetry of action, 150 286–291, 293, 294, 450, 484, 489 ataxia telangiectasia mutated (ATM) allosteric inverse, 42 kinase, 117, 118, 120 full, 100, 200, 209, 255, 283, 286, 289, atomic force microscopy (AFM), 44, 97, 290–292, 294, 330, 390, 394, 398, 401, 98, 140, 417 415, 445, 450 axin, 122, 123 inverse, 14, 15, 20, 30, 32–36, 39–42, 65, 66, 71, 75, 81, 95, 180, 192, 193, 199, β-arrestin signaling, 15–17, 20, 34, 40, 48, 200, 203, 209, 246, 247, 255, 258, 261, 49, 79, 122–125, 127, 173–177, 198, 267, 281, 282, 294, 329–331, 338, 366, 199, 242, 243, 293, 301, 303, 314, 316, 367, 386, 389, 390, 397–399, 405, 435, 317, 467, 468, 473 438, 439, 445, 449, 471, color insert β-catenin dependent signaling fi g. 1.5 (canonical), 120–127, 129 partial, 30, 32, 33, 197, 200, 209, 245, β-catenin independent signaling 246, 255, 258, 261, 268, 290–292, 367, (noncanonical), 120–126 390, 398, 401, 405, 489 β-galactosidase, 175, 176, 196, 199, 307, agonist potency ratios, 17 308, 311, 317, 342, 466 agonist-traffi cking, 292 β-lactamase (BLA), 303, 307–310, 312, AK530, 74 316, 318, color insert fi gure 13.4 AK602, 74 BAPTA, 266 alcuronium, 42, 43, 65, 66, 74, 75, 281 BAY27-9955, 74 allosterism, 11, 40, 47, 70, 71, 72, 75, 99, BAY36-7620, 74 283–288 biased agonism, 65, 261, 268, 270, 271, AlphaScreen, 196, 198, 311 435 amilorides, 73, 74 biased signaling, 255, 270, 292 aminoarylthiazoles, 465 BIBN4096BS, 74 aminobenzothiazoles, 465 bimolecular fl uorescence AMN082, 74, 282, 293 complementation (biFC), 140, 149, ancriviroc, 74 151, 153, 228 angiotensin receptor binding cooperativity (γ), 14, 28, 33, 42,

AT1, 37, 142, 260, 344, 404, 405 65, 69, 80

AT2, 142 bioluminescence resonance energy antagonist transfer (BRET), 44, 46, 98, 139, allosteric, 10, 41, 67, 78, 128, 277–280, 143, 145, 147, 149, 151–153, 171, 282, 286, 293, 294, 450 195, 199, 226, 227, 234–240, 242, competitive, 9, 67, 68, 69, 70, 71, 215, 303 276, 280, 281, 316, 486 biphenyl-indanone A, 74 neutral, 30, 32, 33, 41, 209, 212, 213 bitopic or bivalent ligand, 43, 66, 67, 75, noncompetitive, 9, 67, 420, 489, 490 81 antalarmin, 74 Blomstrand osteochondrodysplasia aplaviroc, 74 (BOCD), 483

appreciable ternary complex (ARB), 29, BMAX (receptor density), 211, 214, 304, 64, 68, 71, 278, 283 305, 328, 350, 354 ARNO (the exchange factor for the bradykinin receptors

small G protein ARF6), 105 B1, 142

ASLW, 74, 282 B2, 142, 265–267, 344

bbindex.inddindex.indd 512512 55/4/2010/4/2010 10:11:2010:11:20 AMAM INDEX 513

brucine, 74, 281 CXCR3, 74 BX-471, 74 CXCR4, 74, 282, 409 CCR1, 74 C7/3-phth, 43, 74 CCR2, 48, 49, 74, 80, 142 Ca2+- and calmodulin dependent kinase CCR3, 74 II (CamKII), 117, 118, 120 CCR5, 19, 48, 49, 74, 76, 80, 142, 277, Ca2+-dependent protein kinase (PKC), 462 117, 118, 120, 301, 483 Cheng and Prusoff equation, 215 calcium (Ca2+) assays, 166, 169, 172, 173, chloramphenicol acetyltransferase 194, 196, 201, 202, 210, 232, 238, 252, (CAT), 307, 308 253, 258, 261, 263, 266, 281, 284, cholecystokinin receptors

289–293, 295, 301, 303, 304, 308, 309, CCK1, 144

312–314, color insert fi g. 7.1 CCK2, 144 calcitonin, 151, 300, 418 cholesterol-rich domains, 103–105 calcitonin gene related peptide (CGRP), chorionic gonadotropin, 79, 99 78, 300 cinacalcet (NPS-1493), 74, 77, 277, 420, receptor, 74 421 calcitonin receptor-like receptor (CRLR circular dichroism, 94, 328, 331, 362 or CLR), 78, 148, 177, 178, color cis-64a, 74 insert fi g. 7.3 coelenterazine, 196, 234, 278 calcitonin receptor (CTR), 78, 148, 153 coiled–coil interaction, 44, 142, 150 calcium sensing receptor (CaR or collateral effi cacy, 65 CaSR), 74, 77, 97, 277, 420, 462, 464, complement C5a receptor, 142 465, 479, 481, 483, 484, 489 conformational selection, 12, 13, 18, 33, Calhex 231, 74 34, 62, 64, 65, 233, 245, 367, 368, 398 cAMP response element (CRE), 198, congenital hypothyroidism, 462, 481, 482 217, 304, 309, color insert fi g. 13.4 congenital morbid obesity, 462, 480 cannabidiol, 74 conopeptide r-TIA, 73 cannabinoid receptors constitutive activity (of a receptor), 14,

CB1, 42, 49, 66, 74, 80, 142, 144, 344 15, 30, 32, 33, 35, 38, 42, 179, 180,

CB2, 413, 448 246, 282, 331, 338, 367, 461, 472, 481 carazolol, 35, 325, 366–368, 370, 389, 390, cooperativity 391, 394, 398, 399, 405, 407, 408, 409, activation (δ), 33, 42, 65 411, 412, 414, 436, 438, 439, 442, binding (γ), 33, 65 443, 444, 445, 448, 449, color insert constant (α; aka cooperativity factor), fi gs. 15.1, 15.3, 15.5, 16.1 10, 28, 33, 42, 63, 64, 68–71, 278, 280, carbachol, 259, 294 283 carvedilol, 246, 247 negative, 41, 42, 47–49, 63, 69, 71, 80, casein kinase 1 and 2 (CK1/2), 117, 118, 99, 100, 128, 150, 215, 278, 286, 289 120, 124, 125 net parameter (αβ), 283, 286–289 caveolin, 34, 79, 103, 104 neutral, 41, 42, 64, 70, 278, 286, 292 CDPPB, 74, 281 positive, 8–11, 41, 42, 47, 63, 69, 150, cell polarity, 114, 121 278, 289 cellular context, 192, 245 corticotropin releasing factor (CRF) CGP7930, 74, 179 receptor, 76, 148, 418 CGP13501, 74 CP-481715, 74 chemokine receptors CP55940, 42, 66 CXCR1, 74, 142, 349 CPCCOEt, 74, 281, 282 CXCR2, 74, 76, 142 CPPHA, 74

bbindex.inddindex.indd 513513 55/4/2010/4/2010 10:11:2010:11:20 AMAM 514 INDEX

cross linking studies, 46, 143, 147, 417 electrochemiluminescence technology cyanopindolol, 35, 325, 364, 368, 370, 399, (ECL), 311 405, 412, 437, 439, 445 electron cryomicroscopy (cryo-EM), 327, cyclic AMP (cAMP) accumulation, 30, 332, 337 78, 105, 152, 166, 169, 171–173, 180, electron paramagnetic resonance (EPR), 193, 195, 198, 210, 216–223, 238, 338, 339, 401, 402 252, 253, 261, 263, 267, 281, 292, 293, electroretinogram (ERG), 470, 475 295, 301, 303, 304, 309–312, 317, 318, EM-TBPC, 74 364, 467, 468, 481, 483, color insert endothelin receptors

fi gs. 7.1, 13.5, 13.8 ETA, 74, 144, 260, 264

cyclic AMP-dependent kinase (PKA), ETB, 144, 462, 482 117, 118, 120, 216, 217, 220, 242, 261, epidermal growth factor (EGF) receptor, 301, 311, 467, 483 117, 194 cysteine-rich (C-rich) domain (CRD), 37, epitope tags 38, 114, 116, 128, 449, 450, 452 1D4, 326, 354 biotin, 354 D2N, 92, 93, 95 FLAG, 354 DCB, 74 His, 354 DeepBlueC, 234 strep, 354 designed ankyrin repeat proteins TAP, 354 (DARPins), 356–358 equilibrium binding assay, 68–70 DFB, 74, 294 ERK1/2 activation or phosphorylation, dielectric spectroscopy, 204 16, 17, 34, 118, 120, 281 differential scanning calorimetry, 204, ezrin, 101, 102 362 dishevelled (DVL), 114, 115, 117, familial exudative vitreoretinopathy 122–127, 129 (FEVR), 128, 462, 484 DMP696, 74 familial glucocorticoid defi ciency (FGD), DmeoB, 74 462, 480 dopamine receptors familial hypocalciuric hypercalcemia

D1, 49, 74, 144, 404, 405 (FHH), 484

D2, 49, 74, 93, 99, 142, 144, 153, 168, fendeline, 74 267, 346, 417, 438 fentanyl, 412

D3, 74, 144, 171, 172, 269, 401, 413, 447 FERM domain, 101, 102 double electron–electron resonance fl uorescence polarization (FP), 222, 305, (DEER), 339 311, 314 DRY/ERY motif, 35, 39, 40, 95, 116, 334, fl uorescence resonance energy transfer 368, 480 (FRET), 30, 32, 44–46, 48, 98, 139, DU124183 (2-cyclopentyl-4- 140, 143, 145, 147, 149, 151, 202, 226, phenylamino-1H-imidazo[4,5-c] 227, 229–247, 308, 309, 402, 419, quinoline), 73, 76 color insert fi g. 13.4 dwarfi sm, 462 fl uorescent spectroscopy, 30 follicle-stimulating hormone (FSH), 38, electric cell-substrate impedance sensing 476, 488 technology (ECIS™), 254, 261–263 receptor (FSHR), 38, 39, 100, 462, 476, effi cacy, 5–7, 10–12, 14, 15, 17–20, 27–30, 481, 482 32, 33, 35, 41–44, 63–67, 70, 71, 73, frizzled receptors

75, 79, 81, 200, 209, 210, 245, 267, FZD1, 114, 115, 118, 126

270, 281–286, 289, 295, 318 FZD2, 114, 115, 118, 126, 127

bbindex.inddindex.indd 514514 55/4/2010/4/2010 10:11:2010:11:20 AMAM INDEX 515

FZD3, 114, 115, 117, 118 gonadotropin-releasing hormone

FZD4, 114, 115, 118, 120, 125, 128, 484, receptor (GnRhR), 74, 462, 464, 465, 485 476–479, 486–488

FZD5, 114, 115, 118, 128, 129 GPCR ligand database (GLIDA), 413

FZD6, 114, 115, 118 GPR1, 167, 169, 175

FZD7, 114, 115, 118 GPR4, 180

FZD8, 114–116, 118 GPR17, 167, 169, 170

FZD9, 114, 115, 118 GPR18, 167, 169

FZD10, 114, 115, 120 GPR20, 171 functional selectivity, 18, 65, 67, 292, GPR22, 171 415 GPR26, 171 furan-1, 74 GPR30, 180 GPR34, 167, 169 G protein-coupled receptor kinases GPR35, 167, 169 (GRKs), 117, 174, 198, 199, 242, 301, GPR37, 171, 177, 178, color insert fi g. 7.3 304, 314 GPR39, 180 G protein independent signaling, 16, 17, GPR43, 74 105, 124, 125, 174, 176, 293 GPR50, 171, 177, 181, color insert fi g. 7.3

GABAB receptors, 38, 44, 45, 48, 74, 79, GPR55, 167, 169 96, 97, 142, 148, 176–179, 181, 276, GPR56, 171, 177, 178, color insert fi g. 7.3 293, 294, 418, 420, 449 GPR65 (TDAG8), 180

GABAB1, 44, 45, 176, 177, color insert GPR68 (OGR1), 180 fi g. 7.3 GPR75, 167, 169

GABAB2, 44, 45, 176–179, 181, color GPR77, 167, 169, 174, 175 insert fi g. 7.3 GPR78, 171 galanin receptors, 144 GPR84, 167, 169 gallamine, 43, 74, 75, 281 GPR81, 172 gastric inhibitory polypeptide receptor GPR85, 170, 172 (GIPR), 148 GPR87, 167, 169, 174 GH-releasing peptide 6, 74 GPR92, 167, 169 glucagon receptor, 74, 300, 418 GPR109b, 170 glucagon-like peptide 1 (GLP1) GPR119, 167, 169 receptor, 74, 76, 77, 148 GPR120, 167, 169, 174 glutamate receptors GPR132 (G2A), 180 mGluR1 (GRM1), 38, 45, 74, 77, 148, GPR161, 172 281, 282, 388, 420, 437, 449–452, GPRC5A, 172 color insert fi g. 16.5 GPRC6A, 167, 169, 170, 173 mGluR2 (GRM2), 74, 77, 284, 420, GS39783, 74 438, 449, 452 GTPγS assay, 125, 169, 173, 174, 195, 210, mGluR3 (GRM3), 388, 420, 437, 212, 227, 238, 252, 253, 267, 282, 289, 450–452 290, 292, 295, 303, 306, 307, color mGluR4 (GRM4), 74, 78, 282, 420, insert fi g. 13.3 449, 452 mGluR5 (GRM5), 37, 45, 74, 77, 148, heparin, 74, 354 281, 282, 294, 420, 421, 450 heterodimer/heterodimerization, 44–46, mGluR7 (GRM7), 74, 282, 293, 388, 48, 49, 79, 80, 96, 99, 100, 142, 420, 437, 450 171, 172, 176–181, 193, 271, 417, glycogen synthase kinase 3 (GSK3), 117, 435 120, 122, 123 HierDock, 448

bbindex.inddindex.indd 515515 55/4/2010/4/2010 10:11:2010:11:20 AMAM 516 INDEX

high-content screening (HCS), 303, 315, KD (dissociation constant), 211–215, 279, color insert fi g. 13.7 280

high-throughput screening (HTS), 192, Ki (inhibition constant), 21, 211, 215 193, 195–204, 215, 220, 222, 223, 253, KB-752, 95 255, 269, 271, 276, 277, 293, 295, 302–319, color insert fi gs. 13.1, 13.3, L-168,049, 74 13.5 L-692,429, 48, 74 Hill slope, 4, 72, 215 L-AP4, 282, 293 Hirschsprung disease (HSCR), 462, 482 L-prolyl-L-leucylglycinamide, 74 histamine receptors Langmuir adsorption isotherm, 3, 4, 6,

H1, 144, 265, 404 28

H3, 35, 144 leukotriene B4 receptors

H4, 144 BLT1, 46, 341–343 HIV inhibitor, 19, 76, 277, 462 ligand-bias, 314, 435 homodimer/homodimerization, 20, 45, ligand-directed traffi cking of receptor 49, 79, 80, 96, 99, 139, 148, 153, 176, stimulus (LDTRS), 33, 34 271, 417, 435 ligand-guided modeling (LGM), 390, hyperparathyroidism, 77, 277, 420, 484 392–394, 396–398, 401, 412, 414, 422, color insert fi g. 15.3 idiopathic hypogonadotropic lipid rafts, 101, 103–105 hypogonadism (IHH), 461, 462, 464, low-density lipoprotein receptor-related 465, 476–479, 488 protein (LRP5/6), 122 inhibitory concentration 50% (IC50), LUF 5484, 73 213–215, 261, 269, 271, 286, 289, 309, luteinizing hormone receptor (LHR), 74, 312, 315, 317, 318, color insert 99, 462, 476 fi gs. 13.4, 13.5, 13.7 lutropin receptor (LTR), 79, 417 IDTA-3x, 76 LY-181837, 74 ifenprodil, 11 LY2033298 (3-amino-5-chloro-6- inactivation no-after potential-D (InaD) methoxy-4-methyl-thieno[2,3-b] mutation, 103 pyridine-2-carboxylic acid International Union of Basic and cyclopropylamide), 41, 74–76, 284 Clinical Pharmacology (IUPHAR), LY 487379, 74 114, 179 IP-10, 74 male pseudohermaphroditism, 462, 482 I-TAC, 74 maraviroc (UK-427,857), 74, 76, 277 impedance, 252, 254, 256, 259, 261–271 mastoparan, 94, 95 iperoxo, 43 McN-A-343, 67, 74, 75 isothermal titration calorimetry, 204 MCPG, 437, 451, 452 mechanic calculations (MC), 417 janus kinase (JAK), 117, 119–121 melanocortin receptors JNJ 16259685, 74 MC1, 144, 462, 481 MC2 (ACTH receptor), 462, 480, 481

KA (equilibrium dissociation constant of MC3, 144, 462, 480 orthosteric ligand), 8, 9, 11, 28–30, MC4, 32, 144, 462, 479, 480, 487 33, 42, 63, 64, 68, 69, 71, 72, 278, 282, melatonin receptors

283, 285 MT1, 144, 171, 177, color insert fi g. 7.3

KB (equilibrium dissociation constant of MT2, 144 allosteric ligand), 9, 11, 28, 29, 42, 63, Membstruk, 403, 448 64, 69, 71, 72, 278–281, 283, 285–289 metarhodopsin I (MI), 104, 330, 331, 337

bbindex.inddindex.indd 516516 55/4/2010/4/2010 10:11:2010:11:20 AMAM INDEX 517

metarhodopsin II (MII), 97, 98, 104, 330, nephrogenic diabetes insipidus (NDI), 331, 338, 339 462, 464, 465, 467–470, 486, 489 MiniMotif Miner, 115, 117, 118 neurokinin NK1 receptor, 38, 39, 74, 144, MMPIP, 74 231, 404, 413 modeling by omission, 411 neuropeptide receptors

models Y1, 37, 144

allosteric ternary complex (ATCM), Y2, 144

28, 41, 42, 63, 64, 68–71, 75, 278–281, Y4, 144

283, 286–288 Y5, 144 allosteric two-state (ATSM), 28, 42, 43, neurotensin receptor (NTS1 or NTR), 64, 71, 282 47, 144, 342, 349, 355 C-terminal latch, 90–96 nonspecifi c bystander effect, 139, 140, collision coupling, 93, 101, 239 240 cubic ternary complex, 14, 15, 28, 32, 33 norrin, 116 extended ternary complex, 13–15, 33 NPS 467, 74 gear-shift, 90–92, 94, 95 NPS 568, 74, 484, 489 ionic lock, 39, 40, 95, 333, 334, 339, 367, NPS 2143, 74, 484 368, 370, 371, 417, 444, 445, color NPS 2390, 74 insert fi g. 16.2 NPXXY motif, 35, 39 lever-arm, 90–92, 94, 95 nuclear factor of activated T-cell sequential fi t, 92, 93, 96, 100 (NFAT), 198, 304, 308, 309, 312, ternary complex (TCM), 13, 14, 28, 32 color insert fi g. 13.4 toggle switch, 39, 40, 416, 442–444, 447, nuclear magnetic resonance (NMR) color insert fi g. 16.1 spectroscopy, 327, 393, 418 moesin, 101, 102 null method, 8, 11 molecular dynamic (MD) simulation, 402, 416, 438 oleamide, 74 MPEP, 37, 74, 128, 282, 294 opioid receptors MT3, 74 κ-OPR, 49, 100, 142, 144, 146, 150 MT7, 74 μ-OPR, 14, 49, 74, 80, 142, 144, 146, MTEP, 74 349, 404, 412 muscarinic acetylcholine receptors δ-OPR, 49, 74, 80, 100, 142, 144, 146, (mAchR) 150, 401, 447, 478, 484, 489

M1, 43, 67, 74, 75, 144, 259, 281, 294, opsin, 46, 98, 146, 148, 243, 325, 329–331, 447 337–339, 348, 385, 397, 403–405, 407,

M2, 42, 43, 66, 67, 69, 74, 144, 280, 396, 416, 417, 436, 440, 443, 444, 446, 447, 397, 404 471–475, 489, color insert fi gs. 16.2,

M3, 43, 74, 144 16.3

M4, 41, 43 67, 74–76, 267, 284 optical biosensors, 204, 259, 261, 262, 268,

M5, 43, 74, 294 269 orexin receptor, 49, 80, 142 N-acetyl-glucosamine-thiazoline, 466 ORL-1 receptor, 168 N-desmethlyclozapine, 75 Org 27569, 42, 66, 74 N-Wasp, 101 Org 27759, 74 nanodiscs, 97 Org 29647, 74 NBI 27914, 74 Org 41841, 74 NBI 35965, 74 Org 43553, 74 NECA (5′-N-ethylcarboxamidoadenosine), ovarian dysgenesis, 462, 482 365 oxytocin receptors (OTR), 146, 346

bbindex.inddindex.indd 517517 55/4/2010/4/2010 10:11:2010:11:20 AMAM 518 INDEX

p70 S6 kinase, 117, 118, 120 radixin, 101, 102 p90 S6 ribosomal kinase (RSK), 117 receptor activity modifying proteins p115RhoGEF, 101 (RAMPS), 20, 78–80, 177, 178, 417, palmitoylation, 116, 329 color insert fi g. 7.3 parathyroid hormone receptor, 17, 148, receptor occupancy, 5, 6, 8, 9, 28, 210 151, 229, 231, 243, 244, 245, 300, 418, receptor reserve, 200, 245 462, 483 receptor theorists PathHunter, 175, 176, 303, 304, 317, 318, Everhardus J. Ariens, 5 color insert fi g. 13.8 Sir James W. Black, 7, 10, 71, 282 PD117975, 281, 282 Alfred.J. Clark, 2, 3, 4, 5 PD81723, 73, 282 Tommaso Costa, 19, 42 PDZ domain, 79, 102, 103, 114, 115, 117, Andre DeLean, 13 123, 129 Paul Ehrlich, 2 pertussis toxin, 95, 125, 240, 257, 258 Frederick J. Ehlert, 10, 41 phospholipase C (PLC), 101, 103, 106, John Henry Gaddum, 9 126, 177, 194, 198, 258, 293, 301, 304, Archibald V. Hill, 3 309, 312, 313, 483, color insert fi g. 13.4 John Newport Langley, 2 phosphorylase kinase, 117, 119, 121 Irving Langmuir, 3, 4, 6, 28 pilocarpine, 2, 66, 67 Henri Louis Le Chatelier, 12 pituitary adenylate cyclase-activating Paul Leff, 7, 10, 32, 71, 282 polypeptide (PACAP)/vasoactive H. Ongun Onaran, 19 intestinal peptide (VIP) receptor, Robert P. Stephenson, 5, 6, 7 18, 78, 148, 418 regulators of G protein signaling (RGS) pleckstrin homology domain, 101 proteins, 79, 88, 106 plerixafor, 74 renilla luciferase, 153, 234, 310 PNU-69176E, 74 reparixin, 74 polo-like kinase (PLK), 117, 119, 121 reporter assays, 169, 172, 173, 175, 198, PREDICT, 403, 448 199, 201, 210, 252, 253, 281, 302–310, prichosanthin, 74 312, 316, 318, 367, color insert probe dependence, 41, 66, 75, 76, 81, 281 fi g. 13.4 propranolol, 34, 398 retinitis pigmentosa (RP), 32, 461, 462, prostaglandin receptors 464, 465, 470–475, 487, 488 PR, 146 rhoA, 101, 194

EP1, 146 rhodopsin (Rho), 35, 40, 44, 47, 48, 89, TPα, 146 90, 92, 95, 97–99, 101, 103–105, 146, protean agonism, 30, 33–35 165, 242, 245, 325, 327, 329–340, 342, protease-activated receptors, 38 343, 353, 356, 358, 359, 362–364, PSNCBAM-1, 74 366–368, 371, 385–387, 389, 392, 396, purinergic receptors 399–405, 407–412, 416–418, 421, 435,

P2Y1, 74, 142, 146 436, 438, 440–448, 453, 462, 464, 465,

P2Y2, 142 470–475, 479, 487–489, color insert

P2Y5, 167, 169 fi gs. 14.3, 15.5, 16.1–16.3

P2Y10, 167, 169, 170 Ro 01–6128, 45, 74

P2Y11, 146 Ro 67–6221, 74 Ro 67–7476, 74 R214127, 74 Rosenthal plot (or Scatchard plot), 214, R-PIA (R-(−)-N6-(2-phenylisopropyl)- 215 adenosine), 281, 282 RSVM, 74, 282 R-spondin, 116 RTI-371, 74

bbindex.inddindex.indd 518518 55/4/2010/4/2010 10:11:2010:11:20 AMAM INDEX 519

SB 656933, 74 TASSER, 403 SCARE algorithm, 388, 411, 421 taste receptors, 45, 48, 79, 96, 114, 142, SCH 351125, 74 148, 176, 179, 449, 452, 461 SCH 527123, 74 TBPB ((1-(1′-2-methylbenzyl)-1,4′- Schiff base, 329, 330, 334, 335, 337, 338, bipiperin-4-yl)-1Hbenzo[d] 471, color insert fi g. 14.3 imidazole-1(3H)-one), 75 Schild analysis, 280, 289 TCAT motif, 90, 94 scintillation proximity assay (SPA), thiochrome, 74 195, 221, 303, 304–307, color insert three-dimensional (3D) model or fi g. 13.3 structure, 324, 327, 328, 332, 333, 337, secretin receptor, 138, 140, 148, 151, 152, 352, 361, 386, 388, 389, 402, 421, 438, 419, color insert fi g. 15.7 447, 448 serotonin receptors thromboxane receptors

5-HT1A, 146, 168 TPα, 146, 462

5-HT1B, 74, 146 TPβ, 146

5-HT1D, 74, 146 thyrotropin or thyroid stimulating

5-HT2A, 74, 177 hormone receptor (TSHR), 15, 79,

5-HT2C, 34, 74, 146, 153, 347 80, 99, 146, 462, 481

5-HT4, 146, 153 thyrotropin releasing hormone

5-HT7, 74 receptor SIB1893, 74, 282 TRHR1, 146, 349 site-directed mutagenesis, 77, 329, 339, TRHR2, 149 347, 417, 440, 448 time-resolved fl uorescence resonance site-directed spin labeling combined with energy transfer (TR-FRET), 195, EPR (SDSL-EPR), 338, 402 222, 310, 311 smoothened (SMO) receptor, 114, 125, timolol, 325, 367, 399, 405, 412, 437, 439, 177, 179, 461, 462, 465, 479, 484, 448 color insert fi g. 7.3 transducin, 34, 90, 92, 97, 98, 101, 125, sodium salicylate, 74 336, 339, 446, 485 soluble FZD-like proteins (sFRPs), Transfl uor assay, 316, 116 transient receptor potential (TRP) somatostatin receptors channel, 103 SSTR1, 146 trichosanthin, 74 SSTR2, 144, 146 trimethylammonium, 5, 67, 352 SSTR3, 146 SSTR5, 144, 146 UCB35625, 74 spin labeled mutants, 94, 338, 339 ultra-high-throughput screening (uHTS), stabilised receptors (StaRs), 363, 364 302–316, 318, 319, color insert staurosporine, 74, 258, 281 fi gs. 13.1, 13.3 stimulus-traffi cking, 65 universal screening approach, 198, 199, 204, 257 tau (τ), 7, 8, 11, 17, 71–73, 283–289 T-0632, 74 vasopressin receptor

TA-2005, 414, 415 V1a, 80, 146, 447

tacrine, 74 V2, 146, 462, 464, 465, 467–470, 479, TAK779, 74 484, 486, 489 TAKK220, 74 venus fl ytrap (VFT) domain, 37, 38, TANGO, 166, 175, 303, 304, 316, 317, 44–46, 77, 142, 449, 450–453 color insert fi gs. 7.1, 13.8 vicriviroc, 74

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virtual ligand screening (VLS), 387, 388, W84, 74, 280 394, 395, 396, 397, 398, 399, 400, 401, WIN 62,577, 74 405, 407, 409, 410, 411, 413, 422, WNTs, 113, 114, 116, 117, 120–130, color insert fi g. 15.3 485 VU0080421, 74 VU0155041, 74 X-ray crystallography or X-ray VU10010 (3-amino-N-(4-chlorobenzyl)- diffraction, 98, 324, 327, 332, 333, 4,6-dimethylthieno[2,3-b]pyridine-2- 339, 350, 355, 434, 453 carboxamide), 75 VU5455 (4-methoxy-N-[7-methyl-3-(2- zinc, 73, 74, 353 pyridinyl)-1-isoquinolinyl] ZM241385, 325, 365, 369, 370, 399, 405, benzamide), 73, 76 407, 412, 437, 440, 442, 443, 449, VU8504, 73 color insert fi gs. 14.8, 16.1

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