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Cambridge University Press 978-0-521-11208-6 - G Protein-Coupled Receptors: Structure, Signaling, and Physiology Edited by Sandra Siehler and Graeme Milligan Index More information Index Α 2A-adrenoceptor D1 receptor interactions, 93 activation kinetics, 148 time-limiting steps, 152–153 allosteric modulators, 257 TR-FRET analysis, 76–78, 84 effector systems, 152 Adenosine-A2, 257 function studies, 55–56 Adenosine-A2A receptor/G protein interaction, activation kinetics, 148, 149 149–150, 151 β/γ complex in adenylyl cyclase signal time-limiting steps, 152–153 modulation, 207–208 -1 adrenoceptors receptors dopamine receptor interactions, 93–94 allosteric modulators, 257 Golf mediation of, 131 cardiovascular regulation role, 291–292 in Parkinson’s disease, 335–338 TR-FRET analysis, 76–78 receptor/G protein interaction, 149–150 2-andrenoceptors receptors schizophrenia, D2R-A2AR heteromeric β 1-adrenoceptors receptor complexes in, 94 polymorphisms in heart failure, Adenylyl cyclases regulation 304–305 as assay, 235 conformational selection in, 275 crystal structures, 203 α 1B-adrenoceptor-G 11 function studies, expression patterns, 191–192, 203–204 57–58 GPCR interactions, direct, 205, 206, ABC294640, 392 217–218 ABC747080, 392 Gq/G11 family, 135–136 ABP688, 257, 260 group I, 195–196 AC-42, 257 group II, 196–197 Acebutol, 298 group III, 197–198 ACPD group IV, 198–199 1S,3R-ACPD, 339 Gz, 131 trans-ACPD, 327, 328 heterologous sensitization, 192, 199–202 in cognitive disorders, 346–348 history, 192–194 in epilepsy, 338, 339, 352–353, 354, isoforms, 190, 191 361, 362 membrane raft compartmentalization, in schizophrenia, 350 204–205 ACP-tag technology, 81–82 oligomerization, 203–204 ACPT-I, 357–359, 360–363 overview, 125–126, 191, 192, 193, ACT-128800, 391 209–210 Actin, 174–175 posttranslational modifications, 202 Adaptor protein complex AP-2, 220–221 signal complex coordination, 205 Addiction, 99–100, 349–351 signaling, GPCR heterodimer impacts Adenocarcinomas (colonic), 132 on, 206–207 Adenomatous polyposis coli protein (APC) S1P2, S1P3 and, 386–387 axin interactions, 180 S1P4, S1P5 functions in, 387 in Wnt/β-catenin signaling, 400–402 specificity, 207–209 Adenosine-A1 in S1P1 functions, 384–386 allosteric modulators, 257 Adhesion GPCR subfamily, 8, 16–17 allosteric/orthosteric site overlap, 262 ADRA1, 10 415 © in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-0-521-11208-6 - G Protein-Coupled Receptors: Structure, Signaling, and Physiology Edited by Sandra Siehler and Graeme Milligan Index More information 416 Index ADRA2C, 10 AMN082 ADX-47273, 257 allosteric modulation of, 257, 259–260 AFQ056, 338 in anxiety disorders, 357–359 Agmatine, 257 in depression, 360 Agonist potency ratio, 270, 272–273 in glutamate induced IP1 production, AGT (O6-alkylguanine-DNA 258–259 alkyltransferase), 80–81 in pain disorders, 361–363 AIDA AMPA receptors, 325 in epilepsy, 338, 339 Anaphylactic shock, 294 in pain disorders, 342 Ancriviroc, 257 in Parkinson’s disease, 336 Angina, 295–296 AK530, 257 Angiogenesis, S1P1 functions in, 384–386 AK602, 257 Angiotensin II A-kinase anchoring proteins (AKAPs) ERK MAP kinases interactions, 221–223 in adenylyl cyclases signal complex receptor biased agonism in β-arrestin coordination, 205 function regulation, 224, 227 cAMP levels, monitoring, 239 Antagonist bias, 279, 280 Akt/glycogen synthase kinase 3 (GSK3) Antalarmin, 257 activation, dopamine in, 91 Anxiety disorders Akt pathway group 1 mGluRs in, 326–327, 328 activation, β-arrestins in, 224, 226 group II mGluRs in, 344–346 PI3K/Akt signaling, Gq-GRK2 group III mGluRs in, 357–359 interactions in, 179–180 APDC, 347, 353–356 S1P4, S1P5 functions in, 387 Aplaviroc, 257 S1P1 functions in, 384–386 Apolipoprotein A-1 (apo A-1), 33–35, 36 Alcuronium, 257 Apoptosis, sphingolipid rheostat, O6-alkylguanine-DNA alkyltransferase (or sphingosine kinases in, 381–382 AGT), 80–81 APPES, 346 Allosteric agonist (inverse agonist), Arf6, 220–221 Allosteric antagonist (inhibitor), Arginine, DRY motif interactions, 44–45 Allosteric enhancer (potentiator), ARNO, 220–221 Allosteric interaction, Arrestin redistribution assays Allosteric modulation applications of, 232–233 activation cooperativity (δ effects), 254, ArrFP, 237–239 255, 256 overview, 236 allosteric/orthosteric site overlap, Arrestins 256–258, 262 β-arrestins allosteric two-state model of, 250–252, Akt activation, 224, 226 254, 255 conformational selection in, 275 antagonist bias in, 279, 280 desensitization functions, 219–220 binding cooperativity (γ effects), 253, diacylglycerol kinase (DGK) 254, 255 interactions, 223–224 co-agonism, 251 in disease, 226–227 examples of, 254–260 ERK MAP kinases interactions, in functional selectivity, 275–276 221–223, 226–227 (See also Functional selectivity) Frizzled interactions, 221 orthosteric ligand affinity (β effects), function, regulation of, 224–226, 227 252–253 functional selectivity in, 278 overview, 247–248, 262–263 IGF-1 interactions, 221 in Parkinson’s disease, 360–361 LDL interactions, 221 properties of, 252 overview, 218, 227 terminology, PDE interactions, 223 ternary complex model of, 249, 254 receptor conformation by, 219 therapeutic advantages, 260–262 receptor desensitization function, two-state model of, 248–249, 253 219–220 Allosteric modulator, receptor endocytosis function, 220–221 Allosteric site, receptor phosphorylation by, 218–219, Alprenolol, 46–47 290–291 Amiliorides, 257, 262 Smoothened interactions, 221 Aminergic subfamily, 10 TGF-β interactions, 221 L-amino acids, 257 in dopamine receptor interactions, 98 © in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-0-521-11208-6 - G Protein-Coupled Receptors: Structure, Signaling, and Physiology Edited by Sandra Siehler and Graeme Milligan Index More information Index 417 function, overview, 2 structure, subtypes, 288, 289 functional coupling in, 42–43 cardiovascular, respiratory function GPCR-Gα protein fusions, 55 regulation roles, 291–292 Gq-GRK2 signaling, 179–180 overview, 288, 307 GRKs in GPCR phosphorylation, pharmacologic assays, 277–278 binding, 154, 165, 218–219, 290–291 pharmacologic interactions, β-blockers/ in receptor activation, 147–148, 153 βAR SNPs, 305–306 ArrFP, 237–239 polymorphisms, human, 300–307 Arrhythmias, β-adrenergic receptor structure, subtypes, 288, 289 applications, 297–298 therapeutic applications of, 292–298 ASLW, 257 BAF-312, 391 Aspirin, 257 Banerjee, S., 43 Asthma, 293–294, 306–307 ΒARKct in cardiovascular disease, 298, 299 Atenolol, 295 Baroreceptor hypothesis, 295 ATP-binding cassette (ABC) family, 383 Β-arrestins. See under Arrestins AT1 receptor dimerization, 56 Bay27–9955 257 Autoimmune uveitis, β-arrestins in, 226 BAY 36–7620 257, 331, 332 Axin Β-blockers. See Β-adrenergic receptors (βARs) G protein interactions, 180–181 Β-catenin, 180 ligand binding in, 160–162 See also Wnt/β-catenin pathway in Wnt/β-catenin signaling, 400–402 B-cell function Gi2 involvement in, 132, 135 Back-scattering interferometry (BSI), 3–4 S1P1 in, 384–386, 388 Β-adrenoceptors receptors (βARs) Belt model, 34–35 activation, signaling, 290–291 Benzodiazepines, 257, 261, 326, 327 β-1 BEST trial, 306 activation, signaling, 290–291 Β/γ complex activation kinetics, 148 adenyl cyclase interactions β/γ complex in adenylyl cyclase signal direct, 205, 206 modulation, 207–208 group I, 195–196 cardiovascular, respiratory function group II, 196–197 regulation roles, 291–292 group III, 197–198 polymorphisms, human, 300, 301, 302 group IV, 198–199 receptor/G protein interaction, 149–150 heterologous sensitization, 200–201 structure, subtypes, 288, 289 signal modulation, 207–208 β-2 background, 193–194, 217–218 activation, 147–148 binding of, 125 activation, signaling, 290–291 function studies, 55–56 adenylyl cyclase glycosylation, 202 GoLoco domain, 181–182, 183 β-arrestin receptor conformation in, 219 G protein activation kinetics, 150–151 β -arrestins-PDE interactions, 223 Gq-GRK2 signaling, 179–180 binding, conformation changes GRK-arrestin phosphorylation, binding, conferred by, 46, 47 218–219, 290–291 cardiovascular, respiratory function heart rate regulation, 134 regulation roles, 291–292 rgRGS signaling, 170–171 functional coupling in, 38, 40–41 in S1P1 functions, 384–386 GPCR-adenylyl cyclase interactions, BIBN4096BS, 257 direct, 205, 206 Bilateria, 8 GPCR-Gα protein fusions, 55 Bimane fluorescence studies, β2-AR polymorphisms, human, 302–303, binding, 45–46 305, 306–307 BINA, 257 reconstitution, benefits of, 39–40 Bioluminescence resonance energy transfer in respiratory disease, 299 (BRET) structure, subtypes, 288, 289 GPCR-Gα protein fusions, 55 TM3/6 interactions, 45, 46 limitations of, 68–69, 70–72, 115 TR-FRET analysis, 76–78, 84 MOR/DOP receptor/D1 receptor ubiquitination in β-arrestin function interactions, 95 regulation, 225 oligomerization studies, 39 β-3 principles, 69 cardiovascular, respiratory function receptor/G protein interaction studies, regulation roles, 291–292 149–150 © in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-0-521-11208-6 - G Protein-Coupled Receptors: Structure, Signaling, and Physiology Edited by Sandra Siehler and Graeme Milligan Index More information 418 Index Bisoprolol, 296–297 Cardiovascular system functions Blumer, K. J., 39 Gi/Go family, 133–135 Bouvier, M., 39 regulation, βARs in, 291–292 BQCA, 257 RGS-RhoGEFs, 176 Bradykinin B2 receptor, 148 Ca2+ release assay, 235 BRET. See Bioluminescence resonance Carvedilol energy transfer (BRET)
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