Subject Index

l\1 33,255 -- on surfactant secretion 242 - in lipolysis 385 -- on ventilation 244-251 - in the renal system 33-48 - half-life 313 -- blood flow 35 - in inflammation 303-314 -- distribution 33 - inhibition of respiration 246 -- renal diseases 42-48 -- adult animals 251 -- renin release 36 -- fetal hypoxia 248 -- signalling 34, 35 -- in neonates 250 -- tubular transport 39 - interaction with other mediators l\2 receptor -- with excitatory amino acids 414 - l\2A 103,113 -- lung 264,265 -- knockouts 123,408 -- neutrophils 306 - l\2B 103,157,249,252,255,262,311 -- NO 258 -- agonist 413 - metabolism 241 - in endothelium 102 - protective effect -- rat aorta 103 -- in gastric ulcer 196 - in the renal system -- in hearing loss 419 -- distribution 48 -- in ischemia 414 -- tubular transport 48 -- in inflammation 303 l\3 receptor 261,264,313 -- in kidney 46,47 l\3P5PS 130 - reduction of vascular resistance, lung l\Bl\ 4 253 - I-l\Bl\ 264 - regulation of vascular tone, lung l\BC proteins 74, 82 252 l\BT-702 418 - release acidosis, l\TP-induced 84 -- in asthmatics 239 l\Dl\ 6 -- by bacteria 307 adenolytics 42 -- in hypoxic brain 250 -- in bronchoconstriction 239 - adenosine a,J3-methylene diphosphate -- endothelium 107 46 -- kidney 37 - anti adrenergic effect 8 -- renal ischemia/hypoxia 46 - 5' -p-(fluorosulfonyl)benzoyl adenosine - stimulation of chemoreceptors 247, 344 249,269 - biphasic responses, airway smooth adenosine-brake hypothesis 37 muscle tone 256 adenosine deaminase 5,43,111,124, - effects 196,243 -- on chloride transport 243 adenosine kinase 4, 268 -- endothelial cells 311 adenosine regulating agent, site and -- eosinophils 310 event specific 411 -- on the heart 6-9,22 adenotin 123 -- mast cells 310,311 adhesion protein 343 -- monocytes/macrophages 308-310 l\DP 81,124 -- neutrophils 304-308 l\DPaS 128, 130 436 Subject Index

ADPf3S 128, 130 - ATPyS 80,88, 127, 128, 170, 176, 183 aggregin 128 - f3,y-meATP 54,80,127 AICAR 313 - 2'-deoxyATP 158 airway, hyperresponsive 265 - Mg-ATP 199 airway tone 256 - 2-meSATP 53,54,83,86, 104, 112, - indirect effect of adenosine on 257 131,154,286,331,365,366,395,398, AIT-082 (Neotrofin) 416 399 AK inhibitor 418,421 - 2-MeS-f3,y-meATP 129 Alzheimer's disease 415,416 -N6-methylATP 158 45 - effect 4-aminopyridine 156 -- arrhythmogenic 87-89 AMP 81 -- cancer 200 AMP 579 21,412 -- chronotropic 87-89 analgesic, prophylactic 425 -- electro physical effect 77,79-82 ANAPP3 154 -- excitation effect, heart 77 anesthesia 417-419 -- on vascular tone 74,75,77,108, anesthetic adjuvant 425 194-196 angina pectoris 411 -release 73,74,108,111,362 angiogenesis 13,14,111 -- in bladder 432 angioplasty, balloon 20 -- by LPS/endotoxin 329 antiasthmatic agents 268,412 -- from synaptosomes 177 antidepressants 408 -- by T-lympohocytes 360 antihypertensive agent 408,411 ATP receptor, cytotoxic (see also P2X7) antiischemic agent 411 358-360 antipsychotics 408 ATP/cellular energetics 20 anti thrombotic agents 129,409 ATPase 186 anxiolytics 408 ATP-triggered automaticity 89 AOPCP 5,16 auditory function 419, 420 292, 426 apamin 147,154, 160-162 basophils, PI receptor 264, 265 APNEA 12,255 B-CLL (B-chronic lymphocytic apnea 245,248,250 leukemia) 368 - sleep apnea 417 benzoyl-ATP 185 apoptosis 12,17,114,309,333,345,362 BG 9719 412,427 - mediated 13 BlIP 20 415 apyrase 190 biliary secretion, AR-C 69331-MX 409,425 192,193 ARDS (adult respiratory distress bioformatics 407 syndrome) 268 bladder emptying 422 ARL 66096 129,131 bleeding disorder 130 arrythmia 410,412 blood pressure, systemic 10 - atrial 7 bone cells, purinergic and pyriminergic arthritis, rheumatoid 303,313 receptor signalling 393 aspirin 411 bone remodeling 393, 420 asthma/asthmatics 239,259,270 - effect of 398, 402-404 - allergic 310 bone resorption 368 - antiasthmatic agents 268,412 breathing - bronchoconstriction, by adenosine - fetal 248, 249 265,310 - neonatal 250, 251 - elevated adenosine concentrations in bronchoconstriction, adenosine-induced the BAL-fluid 267 265,266 - response by adenosine 258 BW 1433 383,386 ATN (acute tubular necrosis) 44 BW-A1433 11,12,14,18 ATP 114 BWA-522 424 - a,f3-meATP 53,76, 80, 83, 86, 112, 127,149,150,152,173,176,198,203, 2-CADO 10,13,122,154,176,241,242 293 - induction of apoptosis 309 Subject Index 437 caecum, purinergic signalling 154- co transmission by ATP 160 - cardiovascular system 74 10,38,43, 121, 176,250,408, - in the gut 146,152,153,158,194 415,417 - in the lung 239 cancer 200,423 - in myenteric nerves 175 - lung, P2 receptor 294 - renal sympathetic nerves 54 candida albicans 329 - in sphincters 165 cardiac death, early 411 COX-2 421 cardiac imaging 410,412 - knockout mice 314 cardioprotection 14-22 CP 3269 418 caspase-l 331,364 CP 66713 255,424 caspase-3 13 CPA 10,14,46,121,246,255,263,382, CCPA 9,18,19 420 CD11b/CDI8 adhesion receptor 330 CPT 246 CD23 344 CPX 5,8-10,14,18,20,21 CD36 426 - [3H]CPX 4 CD39 328, 342 CS-747 411 - knockouts 130 CSC 9,14,19,21 CD73 328,337,342 CV-1808 10, 424 CFTR (cystic fibrosis transmembrane CVT-117 41 conductance regulator) 74,81,185, CVT-124 40,47 243,423 - natriuretic/diuretic effect 41 CGS 15943 412,424 CVT-510 7,8 CGS 15943A 44 CVT 3033 412 CGS 21680 10-12,14,19,106,123, cyclic AMP-adenosine pathway 38 242,252,255,258,262,411,416,417, cyclosporin 46,47 424 cystic fibrosis 282,283,409,413 - biphasic effect on respiration 249 cytokines 306,308,323 - partial agonist like 122 cytotoxicity, ATP-mediated 359,360 - [3H] CGS 21680 123 CHA 21,252,418 diabetes 198,199,420 Chagas' disease 197 - animal models 380 chemoreceptors 244,269 - effect of nucleotides 380 chemotaxis 111 - type 1 377 chloride transport 33 - type 2 377-387 chronotropic, negative 7,8 diabetic rats 52 CI-936 416,424 diadenosine polyphosphates 103, 108, 2-CIADP 127,128 292 Cibacron blue 3GA 182 2' -5' -dideoxyadenosine 123 cisplatin 46 3,7-dimethyl-l-propargylxanthine CI- current 81 248 Ct/HC03- exchanger 84,85 5' -amino-5' -deoxyadenosine 5 CI-IB-MECA 19,264 17,46, 124, 155, 196, 267, cognition enhancers 408 305,411,417 colon diseases (see syndromes) - AI/A2B receptor 162 m-DITC-ADAC 7 - purinergic signalling 160-165 DMPX 8,9 combinatory chemistry 407 DPCPX 37,38,40,45,242,246,248, complement component C2 309 250,266 G 182 DPMA 14 COPD (chronic obstructive pulmonal DPSPX 37,38,255,269 disease) 413,425 dromotropic, negative 6,7 coronary artery bypass graft 411 dry eye disease 419 coronary flow 21,22 DWH 146 412 coronary heart disease 411 coronary hyperemia, hypoxia-induced ecto 5' -nucleotidase 4,37,38,41,46,51 11 ecto-ADPase 41 438 Subject Index 74, 107 - transport inhibition 86 - in granulocytes 337 GP-I-515 268 - in lymphocytes 342, 343 GP 515 421 - in monocytes/macrophages 328 GPCR (G-protein-coupled receptors) EDHF (endothelium-derived oligomerization 426 hyperpolarising factor) 101, 106, 107 GR 79236 18, 382-384, 420, 424 ED RF (endothelium-derived relaxing granulocytes 335-338 factor) 101 - degranulation 338 EHNA 5,21,37 granulomas 368 endothelial cells, sensors of local gut, purinergic signalling 141-204 fluctuations in oxygenation 110 endothelium, roles of and hearing loss 419 101-115 heart failure 254 endotoxemia 47 - congestive 412 248,249,267,311 hemorrhage intraoperative 410 eosinophils 2-HE-NECA 10,19 - A3 receptor on 310 f3-hexaminidase release 263 - PI receptor on 264 155 EPI2010 413 hexokinase 330 epilepsy 415 Hirschsprung's disease 197,198 epithelial cell transport, purinergic histatin 329 signalling 191, 192 - [3H] NECA 122,123 erectile function 422 homocysteine 4 erythrocytes 108 - I-homocysteine 5 erythrocytosis, transplantation-induced 5-HT 124 51,52 HTS (high throughput screening) 407, erythropoietin 49-51 426 hyperglycemia, chronic 379 Fas 13 hypertension 48 FCERI receptor 260, 261 - hypertensive crisis 410 fibroblast, P2 receptor 293 - pulmonary 253,254 FK-453 38,40,43,45,412,424 hypertrophy, cardiac 89,90 FK-838 386 hypothyroidism 46 food intake 200 5 FR113452 40 hypoxia 4-6, 107, 111, 245 ganglia, myenteric, purinergic signalling I-ABA 12 170-179 I-ABOPX 264 gastric acid secretion, purinergic IB-MECA 13,18,19,21,309 signalling 186,187 ICAM-1 311 gastric mucus secretion, purinergic ICE 364,365 signalling 188 immune response 347 gastric ulcer 196,197 - involved cells 324, 325 giant cells, multinucleate (MGC) 309, immune system 330 - P2 receptors 323-347 glaucoma 419 -- P2X7 receptor 355 glial cells, enteric, purinergic signalling immunitiy, native/acquired 323 180, 181 impaired platelet response 130 glomerulopathies 56 incontinence, urge urinary 422 glucose infectious disease 421,422 - disposal in muscle, effect of PI inflammation 113,202,203,303-314, receptor agonists 386 323,323,347 - homeostasis 378 - chronic 368, 369 - plasma levels inflammatory bowel disease 313,420, -- effect of nucleotides 380 421 -- effect of PI receptor ligands 383,385 4, 5, 12, 19 - tolerance 379,384 inotropic 8 Subject Index 439

INS 365 413,425,427 LPS-NFICB activation, attenuation by INS 37217 413 oATP 333 insulin release, stimulation by purine lymphocytes 338-346 nucleotides 379, 381 insulin macrophages - effect of PI receptor ligands 383 - adenosine, effect 308 - resistance 379 - alveolar - secretagogues 382 -- PI receptor 265 interferon-y 310,326,327,363 -- P2 receptor 291 interleukine (IL) macular degeneration 420 - IL-1f3 327,333,334,423 mast cells -- pro-IL-l f3 365 - adenosine, effect 310,311 -- release 364-366 - degranulation 12 - IL-6 113,311,402,423 - PI receptor 259-264 - IL-8 113,311 - P2 receptor 292 - IL-10 309,310 MDL 102234 424 - IL-12 309 membrane pores induction by ATP 358 intestinal secretion, purinergic signalling Meniere's disease 419 188-191 2-MeSADP 128,129 5' -iodotubercidin 5 metabolite, retaliatory 14 Ip5I 426 313,314 irritable bowel syndrome (IBS) 203 6-methoxy-2-phenylisatogen 155 ischemia 13,19,199,200 methylxanthines, chronic exposure 249 - cardiac 412 metrifudil 424 ischemic shock, intestinal 199 MOC (multinucleate giant cells) 330 ischemia-reperfusion injury 312 microbial killing 334 - renal 50,51,56 monocytes ischemic preconditioning 14,15,17,114 - effect of adenosine 308-310 ITP 81,109 - recruitment 326 MRS 1191 19,20 JW-VI-08 413 mucocilliary clearance, effect of UTP 290 K+ current 81-83 multinucleated cell formation 367, K+ ATP channel 82, 106, 381 368 KDR 14 mycobacteria KF 17837 416,417 - bovis 360 KFM-19 415 - tuberculosis 329 KFM-19/BIIP 20 424 myocardial infarction 411 KN-62 359,410 myocardial stunning 19 knockouts - A2A receptor 123,408 N-0861 8,21,424 - CD39 130 Na+/H+ antiporter 84,112,185, 192 - COX-2 314 Na+/HCO,- symporter 84 - P2Y 130 NANC (non-adrenergic-non-cholinergic) - P2Y 2-/- 286 - excitatory nerves 142 Kupfer cells 325 - inhibitory nerves 142,147,153 KW-3902 39,44,45,386,424 - transmission 141,149,152,155,156 KW-3905 412 -- enhancement in diabetes 199 KW-6002 416 -- NO modulation 159 NECA 8,10,14,113,122,187,241,252, L-268605 424 255,267,418 leukemia, B-chronic lymphocytic - [3H] NECA 122, 123 leukemia 368 - 2-HE-NECA 10 19 leukocyte development 324 -N6-benzyl-NECA' 263 library diversity 407 necrosis 333 LPS/endotoxin-dependent signalling, neuromodulation, purinergic, clinical effect of nucleotides 326 opportunities 407--427 440 Subject Index neuromuscular junction, purinergic 142 - in platelets 121-124,131 - caecum/taenia coli 154-160 - in the renal system 33-57 - colon 160-165 - signalling - oesophagus 143-146 -- in the cardiovascular system 22 - small intestine 149-154 -- in the heart 16, 22 - stomach 146-149 -- in mast cells 263 neurourology 422,423 P2 receptor neutrophils - blood vessels 78 - adenosine, effect 304-308 - bone cells 393--404 - P2 receptor 292 - in the cardiovascular system 73-90, NF023 410 111 NFAT 331,344,345 - cell adhesion/cell function 330, 337 NK cell function, modulation 344 - cell growth 111, 204, 338, 345, 398, NNC 21-0136 412,424 415 NNC 53-0055 414 - desensitization 170,332, 395, 400 NO (nitric oxide) 10,101,104,109,361 - in differentation 204,345,415 - interaction with adenosine 258,291, - distribution 54, 76 309 - gastric motility 147 - production 11 - granulocytes 335-338 - release 366 - growth factors, interaction 404 normoxia 4, 5 - immune system 323-347 NOS (nitric oxide synthase) 106, 112 - internalization 87 - inducible 366 - in lymphocytes 340-342 NS-398 421 - in mononuclear phagocytes 325, 326 NSAIDs 421 - mucus secretion, effects 286-288 transporter 4 - myenteric neurones 171 -P2T 130 - metabolism 6,107,142 - P2Xl 52,170,171,327,341,342,422 - release 282, 336, 343 - P2X2 52 - P2X4 183, 185,327,336,381 oATP 331,332,341,355,359,361,366 - P2Xs 90,204,421 O2 supply/demand ratio 21 - P2X6 52, 170 ocular function 419, 420 - P2X7 52,182,183, 185,291,327,330, oesophagus 338,344,345,399,414 - purinergic signalling 143-146,186 -- antagonists 359 osteoblasts, P2 receptors 393-398 -- antigen presenting cells 360 osteoclasts 420 -- in apoptosis 362 - ATP/pH response 401 -- and diseases 360, 362 - P2 receptors 399--401 -- identical with P2Z 357 osteoporosis 420 -- and IL-1f3 release 364, 365 -- in intracellular parasite killing 362 P site, intracellular 123 -- and multinucleated cell formation PI receptor 367,368 - in the cardiovascular system 3-23, -- and NO release 366 111 -- response in immune cells 367 - in cell growth 111,204, 338, 345, 398, -- role in the immune system 355-369 415 -- tissue distribution 356 - in differentation 204,345,415 -P2XM 424 - in inflammation 303-314 - P2Yl 56,90,102,103, 104, 106, 127, -in the lung 239-270 130,190,340,395,398 -- alveolar macrophages 265 - P2Y2 56,90,102,106,114,192,201, -- basophils 264, 265 284,287-289,325,326,332,334,336, -- eosinophils 264 340,396,398,419 -- inflammatory airway cells 258, 259 - P2Y4 56,90,192,201,326,332,340 -- mast cells 259-264 - P2Ys 399 -- table 240 - P2Y6 56,90,201,203,326,332,340, - in myenteric nerves 175-177 396 Subject Index 441

- P2Yll 86,334, 336, 338, 340 purine - P2YAC 130 - release, in gut 141 - P2YADP 130 - signalling (see there) - P2Z 357 - , mitochondrial 16 - pharmacological profile 171 - in platelets 124-132 QTc waves, cardiac 408 - in the renal system 52-57 -- tubular transport 55 RANTES 264 - in respiratory system 281-295 reactive blue 2 111, 146, 179, 182,290, -- alveolar macrophages 291 293 -- airway smooth muscle 290, 291 reactive oxygen species 338, 361 -- ciliary beat frequency, effect 288, rebound contraction 156 289 receptors -- fibroblast 293 - Al (see there) -- lung cancer 294 - A2 (see there) -- mast cells 292 - A3 261,264,313 -- neutrophils 292 - ATP, cytotoxic (see also P2X7) -- pulmonary nerves 293,294 358-360 -- surfactant release, effect 289 - CD11b/CD18 adhesion receptor 330 - signalling - FC£RI receptor 260,261 -- enteric glial cells 173 - mitochondrial purinergic 16 -- heart 79,83-85,89 - PI (see there) -- monocytes/macrophages 330-332 - P2 (see there) -- platelets 125 - platelet ADP receptor 127 -- renal system 55 - SUR1 (sulfonylurea receptor 1) 381 -- respiratory epithelium 285 - T cell receptor (TCR) 324 -- smooth muscle cells 75-77 renal diseases 42-48 pacemaker current 7 renal failure pain 202,203,417-419 - acute 43,47 Parkinson's disease 415,416 - chronic 42, 43 parotid gland, purinergic signalling renal vasodilators 412 181-183 renin release PD 115199 14,123,424 - Al receptor 36 PD 81,723 8 - regulation 37-39 periciliary liquid layer 283 reproductive function 422 permeability resealing, endothelial 311 - endothelial 113 resorption activity 401 - increase, by ATP 355 respiration PGF2 109 - adenosine inhibition 246 phagocytes, mononuclear 325 - peripheral modulation 247,248 8-phenyltheophylline (see also 8-PT) 8, respiratory infections 413 45,111,112,146,176,242 retaliatory metabolite 14 PIT 155 retinopathy, diabetic 419 PKA 9 RG 14202 383,384 plasminogen 363 rhinorrhea 413 plasminogen activator 309 ROI 332 platelet ADP receptor 127 RP-2 341 platelet aggregation 124 R-PIA 4,9,14,18,19,122,241,249, - adenosine inhibition 121 250,418,419 - blokade by 121 platelet shape charge 124 SAH hydrolase 5 PPADS 103,152,159,164,170,175, salicylate 314 192,293,345,346,418 scavenger nucleotidase 329 415 SCH 58261 5,7,10,11,123,124,416, 8-PT (see also 8-phenyltheophylline) 424 261 - CH)SCH 58261 4 pulmonary nerves, P2 receptor 293,294 schizophrenia 417 442 Subject Index

SDZ WAG 994 383,384,412,424 - enhancement by adenosine 305, 308 E-selectin 311 143,147,155,160,175,179, L-selectin 344, 368 345,418 SIDS (sudden infant death syndrome) surfactant release 242, 289 251 SVT 425 signalling, purinergic syndromes/diseases - biliary secretion 192, 193 - Alzheimer's disease 415,416 - caecum/taenia coli 154-160 - Chagas' disease 197 - colon 160-165 - Hirschsprung's disease 197, 198 - endothelium 106 - Meniere's disease 419 - enteric glial cells 180, 181 - Parkinson's disease 415,416 - epithelial cell transport 191, 192 - gastric acid secretion 186, 187 tachycardia, supraventricular 410 - gastric mucus secretion 188 taenia coli, purinergic signalling - gut 141-196 154-160 -- diseased gut 196-204 4,20,37,38,44,45,51,87, - intestinal secretion 188-191 121,176,249-251,412,413,415 - myenteric ganglia 170-179 thrombosis 121 - in oesophagus 143, 186 thrombus formation 113 - parotid gland 181-183 tinnitus 419 - salivary secretion 181 TNF-a (tumor necrosis factor-a) 113, - small intestine 149-154 309,310,333,363,414,421 - in sphincters 165-169 TNP-ATP 190,410 - stomach 146-149,186,187 TIP 109 - submandibular gland 183-186 tubular necrosis, acute (ATN) 44 - submucosal ganglia 179, 180 tumours, colonic 200 sinusitis 413 TXA2 124 sleep 417 - sleep apnea 417 UTP 81,290 small intestine, purinergic signalling 146-149 vasodilatation SPA 383,384 - endothelium dependent 103, 104 sphincters, purinergic signalling - coronary 11 165-169 vasodilators, renal 412 8-SPT (see also 8-sulphophenyltheo• VEGF 14,112 phylline) 6,10,14-18,21,252 stomach, purinergic signalling 146-149, wound healing 308,421 186,187 WRC 0470 412 streptozotocin 52 WRC-0571 8 stroke 414,415 - prevention 411 XAC 21 submandibular gland, purinergic XAMR0721 410 signalling 183-186 sulfasalazine 313,314 ZM 241285 9 8-sulphophenyltheophylline (see also ZM 241385 11,111,263,424 8-SPT 196 Zucker diabetic fatty rats 379,384, superoxide anion generation 385