Cholinergic Mechanisms: Function and Dysfunction

Cover......Page 1
Cholinergic Mechanisms: Function and Dysfunction......Page 2
Contents......Page 4
Preface......Page 20
Contributors......Page 22
SCIENTIFIC CAREER......Page 78
RESEARCH, 1968–1974......Page 79
THE FIRST ISCM......Page 80
PERSONAL RECOLLECTIONS......Page 81
REFERENCES......Page 82
FUNCTION......Page 84
ACh-BINDING SITES......Page 85
STRUCTURE OF THE MEMBRANE DOMAIN......Page 86
CHANNEL DYNAMICS......Page 87
RESTING-STATE GATE......Page 89
DESENSITIZED-STATE GATE......Page 90
REFERENCES......Page 91
THE BINDING SITE IN ANIMAL SPECIES THAT ARE RESISTANT TO α-BTX......Page 96
A LEAD PEPTIDE SELECTED BY α-BTX FROM A RANDOM PHAGE-DISPLAY PEPTIDE LIBRARY......Page 97
HAPs DESIGNED BY SYSTEMATIC RESIDUE REPLACEMENT......Page 98
THE NMR STRUCTURE OF A HAP/α-BTX COMPLEX IN SOLUTION......Page 99
THE CRYSTAL STRUCTURE OF A HAP/α-BTX COMPLEX......Page 100
CONCLUDING REMARKS......Page 101
REFERENCES......Page 102
INTRODUCTION......Page 104
IDENTIFICATION OF THE SITES BY WHICH VARIOUS SNAKE TOXINS INTERACT WITH DIFFERENT NICOTINIC ACHR SUBTYPES......Page 105
DETERMINATION OF THE α7 RECEPTOR RESIDUES INVOLVED IN THE α-Cbtx INTERACTION AND IDENTIFICATION OF TOXIN-RECEPTOR INTERACTING RESIDUES BY CYCLE-MUTANT EXPERIMENTS......Page 106
STRUCTURAL MODEL OF THE α-Cbtx-α7 NEURONAL NICOTINIC AChR COMPLEX......Page 107
REFERENCES......Page 108
LIPID SITES AT THE AChR MEMBRANE INTERFACE......Page 110
SECONDARY STRUCTURE OF AChR TM DOMAINS......Page 112
REFERENCES......Page 114
STUDIES AND RESULTS......Page 116
CONCLUSIONS......Page 120
REFERENCES......Page 121
INTRODUCTION......Page 122
STRUCTURE OF THE BOUND α-BTX......Page 123
STRUCTURE OF THE BOUND α1182–202......Page 124
MODELING OF THE AChR-EC/α-BTX COMPLEX......Page 125
LIGAND-BINDING SITE OF AChR......Page 126
BR36 OCCUPIES ACETYLCHOLINE-BINDING POCKET......Page 127
BR36 IS INVARIANT IN SNAKE α-NEUROTOXINS......Page 128
NMR STRUCTURE OF THE α-BTX COMPLEXED WITH α1182–202 ACCOUNTS FOR SPECIES-SPECIFIC SUSCEPTIBILITY TO THE TOXIN......Page 129
REFERENCES......Page 130
USE OF SCANNING MUTAGENESIS TO PROBE THE FUNCTIONS OF AMINO ACIDS IN RECEPTOR SEQUENCES......Page 132
A HOMOLOGY MODEL OF THE M1 MUSCARINIC RECEPTOR......Page 133
THE BINDING SITE FOR ACETYLCHOLINE AND N-METHYL SCOPOLAMINE......Page 134
A LIGAND DOCKING SITE?......Page 135
INTRAMOLECULAR CONTACTS THAT SELECTIVELY STABILIZE THE GROUND STATE......Page 136
TRANSDUCTION OF ACh-BINDING ENERGY INTO RECEPTOR ACTIVATION......Page 137
REFERENCES......Page 138
M1R−/− MICE ARE HYPERACTIVE......Page 140
M2 AND M4 RECEPTORS MEDIATE MUSCARINIC AGONIST-INDUCED ANALGESIC EFFECTS AT SPINAL AND SUPRASPINAL SITES......Page 141
M2 RECEPTORS MEDIATE MUSCARINIC AGONIST-INDUCED DESENSITIZATION OF PERIPHERAL NOCICEPTORS......Page 142
CENTRAL MUSCARINIC AUTORECEPTORS......Page 143
M5 RECEPTORS MEDIATE ACh-INDUCED DILATION OF CEREBRAL ARTERIES AND ARTERIOLES......Page 144
REFERENCES......Page 145
INTRODUCTION......Page 148
ALLOSTERIC PROPERTIES OF MUSCARINIC RECEPTORS......Page 149
INFLUENCE OF MODIFICATIONS IN o2 AND o3 OF M3 RECEPTOR ON ALLOSTERIC CHARACTERISTICS......Page 150
IMPLICATIONS......Page 151
REFERENCES......Page 152
11. René Couteaux (1909–1999) and his presynaptic active zone......Page 154
REFERENCES......Page 156
A STRUCTURE AT MOLECULAR LEVEL RESOLUTION—NICOTINIC RECEPTORS FROM MUSCLE......Page 158
ACETYLCHOLINE-BINDING PROTEIN A SURROGATE FOR THE PENTAMERIC LIGAND-GATED ION CHANNEL......Page 160
ACETYLCHOLINESTERASE—EXTENDING BEYOND STATIC STRUCTURAL TEMPLATES......Page 161
REFERENCES......Page 163
13. Neuronal calcium dynamics: one message with many meanings......Page 164
REFERENCES......Page 167
THE CHOLINERGIC MEDIATOPHORE IS ABLE TO RELEASE GLUTAMATE AS WELL......Page 168
A GLUTAMATERGIC MEDIATOPHORE?......Page 169
TWO CHOICES FOR THE SAME FUNCTION......Page 170
AN UNSUSPECTED DIFFERENCE BETWEEN CHOLINERGIC AND GLUTAMATERGIC SYNAPTOSOMES......Page 171
MEDIATOPHORE IN CHOLINERGIC AND GLUTAMATERGIC BRAIN AREAS......Page 172
POSSIBLE PATHOLOGICAL IMPLICATIONS OF ACh AND GLU CO-RELEASE......Page 173
REFERENCES......Page 174
MOLECULAR EMBODIMENT OF THE Ca-VOLTAGE HYPOTHESIS......Page 176
IN KNOCKOUT MICE LACKING FUNCTIONAL M2R THE TIME-COURSE OF RELEASE IS SENSITIVE TO THE LEVEL AND KINETICS OF [Ca2+]i......Page 177
DISCUSSION......Page 179
REFERENCES......Page 180
INTRODUCTION......Page 182
ATP INDUCES INOSITOL PHOSPHATES AND INTRACELLULAR CA2+ MOBILIZATION IN MUSCLE......Page 183
FUNCTIONAL ROLE OF P2Y1 RECEPTOR IN DIRECTING THE POSTSYNAPTIC GENE EXPRESSION......Page 184
REFERENCES......Page 187
CULTURED HUMAN MUSCLE......Page 190
EXPRESSION OF AChR......Page 192
CONTROL OF FUNCTIONAL NMJ MATURATION IN THE IN VITRO INNERVATED HUMAN MUSCLE: THE ROLE OF AGRIN......Page 193
REFERENCES......Page 194
CHOLINERGIC ALLOSTASIS UNDER STRESS......Page 196
ACHE ALTERNATIVE SPLICING UNDER STRESS......Page 197
AChE-R: THE PRODUCT OF STRESS RESPONSES......Page 198
BIOMEDICAL IMPLICATIONS......Page 199
REFERENCES......Page 200
INDEPENDENT TRANSCRIPTION OF ChAT AND VAChT......Page 202
CIS-ACTIVE CGL ELEMENTS REQUIRED FOR CHOLINERGIC CELL-SPECIFIC EXPRESSION......Page 203
CHOLINERGIC AND NORADRENERGIC PHENOTYPES IN SYMPATHETIC NEURONS AND SWEAT GLANDS......Page 205
CO-EXPRESSION OF THE HIGH-AFFINITY CHOLINE TRANSPORTER WITH THE CGL MEMBERS......Page 206
REFERENCES......Page 207
RESULTS......Page 210
REFERENCES......Page 213
NEURONAL PHENOTYPE COMPLEXITY......Page 214
THE MODEL: P19 EMBRYONIC CARCINOMA CELLS......Page 215
TRANSCRIPTIONAL REGULATORS......Page 217
GENOMICS APPROACH......Page 218
FUTURE PERSPECTIVES......Page 219
REFERENCES......Page 220
22. Miriam M Salpeter (Mika)—biographical notes......Page 222
INTRODUCTION......Page 224
INPUT PARAMETERS AND SCALING ARGUMENTS FOR THE SIMULATION OF MINIATURE POSTSYNAPTIC CURRENTS......Page 225
RESULTS FROM THE TWO CATALOGS AND A SENSITIVITY STUDY......Page 226
AN ASYMMETRY BETWEEN DENERVATION AND REINNERVATION FOR THE NMJ......Page 227
AN INTERMEDIATE RECEPTOR TYPE INSERTED DURING REINNERVATION......Page 228
REFERENCES......Page 230
INTRODUCTION......Page 232
THE SPLICE VARIANTS OF AChE......Page 233
CHOLINESTERASE SUBUNITS OF TYPE T: THE STRUCTURE OF THE T PEPTIDE......Page 235
STRUCTURE OF THE WAT/PRAD COMPLEX......Page 237
CONCLUSION......Page 238
REFERENCES......Page 239
STRUCTURE OF NATIVE hBChE......Page 242
STRUCTURE OF AGED hBChE......Page 243
REFERENCES......Page 245
RESULTS AND DISCUSSION......Page 248
REFERENCES......Page 252
INTRODUCTION......Page 254
STRUCTURAL DETERMINANTS OF E2020 SELECTIVITY FOR HUMAN AChE VS HUMAN BChE......Page 255
CONTRIBUTION OF FUNCTIONAL CHARACTERIZATION OF HUMAN AChE-LIGAND COMPLEXES BY SITE-DIRECTED MUTAGENESIS TO STRUCTURE-BASED DRUG DESIGN......Page 256
REFERENCES......Page 258
RESULTS AND DISCUSSION......Page 260
REFERENCES......Page 263
STRUCTURE OF ace GENES AND THE ENCODED PROTEINS......Page 264
CONCLUSIONS......Page 267
REFERENCES......Page 268
IDENTIFICATION OF DROSOPHILA CHOLINERGIC TRANSCRIPTIONAL REGULATORS......Page 270
INTRODUCTION OF Gal4 SYSTEM FOR STUDYING CHOLINERGIC LOCUS REGULATION......Page 271
WHAT OTHER GENES ARE EXPRESSED IN CHOLINERGIC NEURONS?......Page 272
REFERENCES......Page 274
THE nAChR GENE FAMILY OF CAENORHABDITIS ELEGANS......Page 276
THE nAChR GENE FAMILY OF DROSOPHILA MELANOGASTER......Page 279
REFERENCES......Page 281
DEG-3 IS A NONESSENTIAL GENE......Page 284
THE DEG-3/DES-2 CHANNEL......Page 285
RIC-3 IS NEEDED FOR MATURATION OF nAChRs......Page 286
RIC-3 IS A MEMBER OF A FUNCTIONALLY CONSERVED FAMILY OF PROTEINS......Page 287
OTHER GENES NEEDED FOR DEG-3 FUNCTION......Page 288
REFERENCES......Page 289
INTRODUCTION......Page 290
ENDPLATE CHOLINE ACETYLTRANSFERASE DEFICIENCY......Page 291
ENDPLATE ACETYLCHOLINESTERASE DEFICIENCY......Page 292
KINETIC MUTATIONS OF THE AChR......Page 294
SLOW-CHANNEL SYNDROMES......Page 295
FAST-CHANNEL SYNDROMES......Page 296
AChR DEFICIENCY CAUSED BY MUTATIONS IN AChR SUBUNIT GENES......Page 298
MYASTHENIC SYNDROME CAUSED BY MUTATIONS IN RAPSYN......Page 300
REFERENCES......Page 301
ARTHROGRYPOSIS MULTIPLEX CONGENITA (AMC)......Page 304
‘SERONEGATIVE’ MG (SNMG)......Page 306
REFERENCES......Page 307
INTRODUCTION......Page 310
MUSCARINIC RECEPTOR AUTOANTIBODIES IN SJÖGREN’S SYNDROME INHIBIT PARASYMPATHETIC NEUROTRANSMISSION......Page 311
LOWER URINARY TRACT SYMPTOMS ARE INCREASED IN PRIMARY SJÖGREN’S SYNDROME......Page 312
DO MUSCARINIC RECEPTOR AUTOANTIBODIES IN SJÖGREN’S SYNDROME TARGET CARDIAC TISSUES?......Page 314
SUMMARY......Page 315
REFERENCES......Page 316
INTRODUCTION......Page 318
2. SUPPRESSION OF ONGOING EAMG BY A SYNGENEIC AChR RECOMBINANT FRAGMENT......Page 319
3. EFFECT OF DIRECT MODULATION OF KEY CYTOKINES AND CO-STIMULATORY FACTORS ON THE COURSE OF EAMG......Page 320
REFERENCES......Page 321
CHARACTERIZATION OF THE N-GLYCAN STRUCTURES ASSOCIATED WITH RECOMBINANT AND NATIVE BOVINE AChE......Page 322
EFFECT OF ENZYME TETRAMERIZATION ON THE PHARMACOKINETICS OF rBoAChE......Page 323
HUMAN AChE PHARMACOKINETICS ABIDES BY THE SAME POST-TRANSLATION-RELATED RULES AS BOVINE AChE......Page 325
HuAChE PHARMACOKINETICS IS AFFECTED BY THE NUMBER OF APPENDED N-GLYCANS......Page 328
REFERENCES......Page 329
CHEMICALS......Page 332
MICRODIALYSIS PROCEDURES......Page 333
THERAPEUTIC EFFICACY OF CPA IN OP POISONING......Page 334
CENTRAL ACh RELEASE DURING SARIN OR VX POISONING......Page 335
EFFECT OF PARTIAL A1 AGONISTS ON SARIN-INDUCED EPILEPTIFORM ACTIVITY......Page 336
THERAPEUTIC EFFICACY OF 2DCPA DURING SARIN POISONING......Page 337
THERAPEUTIC EFFICACY OF PARTIAL AGONISTS IN OP POISONING......Page 338
REFERENCES......Page 339
BIOSENSOR SYNTHESIS AND ASSAY......Page 342
COMPARISON OF SOLUBLE AND IMMOBILIZED ENZYMES......Page 343
LONGEVITY OF BIOSENSOR IN AQUEOUS ENVIRONMENTS......Page 344
DIFFERENTIAL DETECTION OF CHEMICAL WARFARE AGENTS......Page 345
CONCLUSIONS......Page 346
REFERENCES......Page 347
MATERIALS AND METHODS......Page 348
RESULTS......Page 349
DISCUSSION......Page 350
REFERENCES......Page 351
INTRODUCTION......Page 354
LIPOPHILICITY......Page 355
PERIPHERAL ANTI-INFLAMMATORY ACTIVITY......Page 356
RATIONALE OF DEVELOPMENT AND SYNTHESIS OF BIFUNCTIONAL COMPOUNDS......Page 357
INHIBITION KINETICS OF AChE AND BChE......Page 358
LIPOPHILICITY......Page 360
INHIBITION OF CYCLOOXYGENASE ISOENZYMES IN VITRO......Page 361
ANTI-INFLAMMATORY ACTIVITY IN BRAIN......Page 362
PROTECTION AGAINST CLOSED HEAD INJURY (CHI)......Page 363
REFERENCES......Page 364
42. In memoriam: Miroslav Brzin (13 April 1923–8 August 1999)......Page 366
AChE ACCUMULATION IN THE NEUROMUSCULAR JUNCTION......Page 368
MUSCLE FUNCTION INFLUENCES AChE EXPRESSION IN MUSCLES......Page 371
REFERENCES......Page 372
INTRODUCTION......Page 374
POTENTIATION BY GALANTAMINE OF ACh-INDUCED RESPONSES IN HEK293 CELLS STABLY EXPRESSING DIFFERENT nAChR SUBTYPES......Page 375
GALANTAMINE, ACTING AS A NICOTINIC APL, FACILITATES GLUTAMATERGIC TRANSMISSION IN RAT HIPPOCAMPAL SLICES......Page 376
ChE INHIBITION DOES NOT CONTRIBUTE TO THE POTENTIATING EFFECTS OF GALANTAMINE ON SYNAPTIC TRANSMISSION IN THE MAMMALIAN BRAIN......Page 379
WHY ChE INHIBITION PER SE DOES NOT INCREASE THE ACTIVITY OF ALL nAChRs IN THE BRAIN33 CHOLINE AS A FULL AGONIST AT α7 nAChRs......Page 380
SUMMARY AND DISCUSSION......Page 381
REFERENCES......Page 383
INTRODUCTION......Page 386
PSAB-OFP: A COMMON AGONIST OF 5-HT3Rs AND α7 nAChRs......Page 387
CONCLUSION......Page 390
REFERENCES......Page 391
INTRODUCTION......Page 394
KNOCKOUT MICE LACKING β2 AND/OR β4 SUBUNITS......Page 395
ANTONOMIC FUNCTION OF NEURONAL nAChR SUBUNITS......Page 396
REFERENCES......Page 398
INVOLVEMENT OF THE SEPTOHIPPOCAMPAL ACh SYSTEM IN EYEBLINK CONDITIONING......Page 400
SEPTOHIPPOCAMPAL ACh SYSTEM AND HUMAN NEUROPATHOLOGY......Page 401
GALANTAMINE AND ALLOSTERIC MODULATION......Page 402
GALANTAMINE AND EYEBLINK CLASSICAL CONDITIONING......Page 403
SUMMARY AND CONCLUSIONS......Page 404
REFERENCES......Page 405
DISTRIBUTION OF MUSCARINIC RECEPTOR SUBTYPES......Page 408
SYMPTOMS OF SCHIZOPHRENIA AND ASSOCIATED BRAIN REGIONS......Page 409
POST MORTEM ANALYSIS AND IN VIVO IMAGING OF MUSCARINIC RECEPTORS......Page 410
STUDIES IN ANIMALS IMPLICATING ROLE OF MUSCARINIC RECEPTORS IN SCHIZOPHRENIA......Page 411
DOPAMINE AND ACh RELEASE......Page 412
ELECTROPHYSIOLOGY......Page 413
COGNITION......Page 414
CLINICAL STUDIES WITH MUSCARINIC AGONISTS IN SCHIZOPHRENIA......Page 415
CONCLUSION......Page 416
REFERENCES......Page 417
THE M1 mAChR AS A THERAPEUTIC TARGET IN AD......Page 422
MODULATION OF Aβ LEVELS VIA M1 mAChR AND COMPARISON WITH SOME OTHER TREATMENTS......Page 424
PREVENTION OF Aβ NEUROTOXIC EFFECTS WITH RELEVANCE TO OXIDATIVE STRESS IN AD......Page 426
REFERENCES......Page 427
EFFECTS OF TV3326, TV3279, RASAGILINE, AND TVP 1022 ON sAPPa RELEASE......Page 430
THE EFFECTS OF PKC, MITOGENACTIVATED KINASE (MEK) AND TYROSINE KINASE INHIBITORS ON THE RELEASE OF sAPPα BY PROPARGYLAMINES......Page 431
ACTIVATION OF MAP KINASE BY TV3326 AND TV3279......Page 432
DISCUSSION......Page 433
CONCLUSIONS......Page 436
REFERENCES......Page 437
AMYLOID DEPOSITION AND THE ROLE OF AChE......Page 440
Aβ/AChE COMPLEXES INDUCE NEURODEGENERATION THAT INVOLVES A LOSS OF FUNCTION OF THE WnT SIGNALING......Page 442
REFERENCES......Page 444
EFFECTS OF APOE ON LIPID SYNTHESIS IN THE PRESENCE AND ABSENCE OF EXOGENOUS LIPIDS......Page 446
EFFECTS OF apoE ON THE INCORPORATION OF EXOGENOUS LIPIDS INTO CELLULAR LIPIDS......Page 447
DISCUSSION......Page 449
REFERENCES......Page 450
CORTICAL CHOLINERGIC TERMINATIONS ESTABLISH CLASSICAL SYNAPTIC CONTACTS......Page 452
CORTICAL CHOLINERGIC PRESYNAPTIC BOUTONS BECOME ATROPHIC WITH AGING......Page 453
THE CORTICAL CHOLINERGIC INPUT MAKES PREFERENTIAL SYNAPTIC CONTACTS ON PYRAMIDAL NEURONS—THE IMPACT OF AGING......Page 454
THE NUMBER OF CORTICAL CHOLINERGIC TERMINATIONS IS DEPENDENT ON ENDOGENOUS NGF AND VULNERABLE TO AMYLOID BURDEN......Page 455
REFERENCES......Page 456
RELATIONSHIP BETWEEN NEUROTROPHIN mRNA EXPRESSION AND AChE-POSITIVE AXONAL INGROWTH......Page 458
PATTERNS OF NEURITE OUTGROWTH FROM CHOLINERGIC NEURONS ‘SEEDED’ ONTO ORGANOTYPIC SLICE CULTURES OF HIPPOCAMPUS AND DENTATE GYRUS......Page 460
CONCLUSIONS......Page 462
REFERENCES......Page 463
EXPLORATION OF A NOVEL ENVIRONMENT AND HABITUATION......Page 464
ACQUISITION OF FEAR MEMORY......Page 467
REFERENCES......Page 469
RESTING CHOLINE PLASMA LEVEL......Page 472
HOMEOSTASIS OF SYNAPTIC CHOLINE IN THE BRAIN......Page 473
REFERENCES......Page 474
INTRODUCTION......Page 476
MICRODIALYSIS AND DETERMINATION OF ACh......Page 477
EFFECTS OF GLUCOSE PLUS CHOLINE ON HIPPOCAMPAL ACh RELEASE IN AGED FVB/N MICE......Page 478
EFFECT OF PRECURSOR AVAILABILITY ON ACh SYNTHESIS AND BEHAVIOR......Page 479
IMPLICATIONS OF PRECURSOR EFFECTS FOR THE CONTROL OF ACh SYNTHESIS......Page 480
REFERENCES......Page 481
INTRODUCTION......Page 482
PROPERTIES OF CHOLINERGIC NEURONS......Page 483
CHOLINERGIC NEURONS IN CULTURE......Page 485
REFERENCES......Page 486
CHOLINERGIC THERAPY OF ALZHEIMER’S DISEASE: HOW DID IT START?......Page 488
CLINICAL DATA SUPPORT A STABILIZING EFFECT OF ChEIs......Page 489
PRECLINICAL DATA SUPPORTING A NONSYMPTOMATIC EFFECT OF ChEIs......Page 490
EFFECTS OF ChEIs ON Aβ METABOLISM NOT DEPENDENT ON ChE INHIBITION......Page 491
CONCLUSIONS: HOW CAN THE LONG-TERM EFFECTS OF ChEIs ON AD......Page 492
REFERENCES......Page 493
SUBJECTS AND METHODS......Page 496
RESULTS AND COMMENT......Page 497
REFERENCES......Page 498
IMAGING AND ANALYSIS......Page 500
REFERENCES......Page 505
ACh AND COGNITION IN AD......Page 508
ACh AND BEHAVIORAL CHANGES IN AD......Page 509
REFERENCES......Page 510
INTRODUCTION......Page 512
ACETYLCHOLINE SYNTHESIS......Page 515
NICOTINIC RECEPTORS......Page 516
MUSCARINIC RECEPTORS......Page 518
CHOLINESTERASES......Page 519
ACETYLCHOLINE RELEASE......Page 520
SJOEGREN’S SYNDROME......Page 522
CHOLINERGIC PATHWAYS......Page 523
COGNITION......Page 524
ACKNOWLEDGMENTS......Page 525
REFERENCES......Page 527
64. A single amino acid substitution found in pirimicarb-insensitive acetylcholinesterase of the peach-potato aphid, Myzus persicae (Sulz.)......Page 530
ACTIVITY......Page 532
REFERENCES......Page 533
66. Nicotine induces glutamate release from hippocampal mossy fiber synaptosomes......Page 536
REFERENCES......Page 538
A ROLE FOR MUSCARINIC RECEPTORS IN HUMAN PD......Page 540
A POSSIBLE GENE-ENVIRONMENT INTERACTION MODEL FOR HUMAN PANIC DISORDER: PRIMING THE FIRST ATTACKS THROUGH THE CHOLINERGIC SYSTEM......Page 541
REFERENCES......Page 542
68. A zebrafish mutant as a model for an acetylcholinesterase-deficientvertebrate......Page 544
REFERENCES......Page 546
DRC OF ACh AND EPIBATIDINE AT hα4β2 nACh RECEPTORS......Page 548
ELIMINATION OF PKC PHOSPHORYLATION SITES IN hα4 SUBUNIT INFLUENCES THE NATURE OF EPIBATIDINE DRC......Page 549
REFERENCES......Page 552
RESULTS AND DISCUSSION......Page 554
REFERENCES......Page 556
71. Role of spontaneous mutations of neuronal nicotinic acetylcholine receptors in ADNFLE......Page 558
REFERENCES......Page 560
RECONSTITUTION IN XENOPUS OOCYTES......Page 562
CONCLUSION AND PERSPECTIVES......Page 563
REFERENCES......Page 565
EXPERIMENTAL APPROACH, RESULTS, AND DISCUSSION......Page 566
REFERENCES......Page 568
74. Cholinergic modulation of chemotaxis in human melanoma cells......Page 570
REFERENCES......Page 572
75. Some considerations concerning the molecular mechanism of cholinesterase catalysis......Page 574
REFERENCES......Page 575
ANATOMY......Page 576
POPULATION ACTIVITY IN SMALL NEURONAL NETWORKS......Page 577
INTRINSIC PROPERTIES......Page 579
REFERENCES......Page 580
RESULTS......Page 584
REFERENCES......Page 585
78. Candoxin: a new snake toxin specific for the α7 nicotinic acetylcholine receptor......Page 586
REFERENCES......Page 587
RESULTS AND DISCUSSION......Page 588
REFERENCES......Page 591
MATERIALS AND METHODS......Page 592
RESULTS AND DISCUSSION......Page 593
REFERENCES......Page 594
MODIFICATION OF ΔC-HuAChE BY PEG......Page 596
PHARMACOKINETIC BEHAVIOR OF PEG-HuAChE......Page 597
REFERENCES......Page 598
RESULTS......Page 600
CONCLUSIONS......Page 601
REFERENCES......Page 602
83. A calcium-proton antiport in presynaptic nerve terminals......Page 604
REFERENCES......Page 606
RESULTS......Page 608
REFERENCES......Page 610
85. A peptide from the C-terminal oligomerization domain of human synaptic (T-form) acetylcholinesterase forms classical amyloid fibrils......Page 612
REFERENCES......Page 614
RESULTS......Page 616
CONCLUSIONS......Page 617
REFERENCES......Page 618
COMBINED USE OF DHEA AND DONEPEZIL......Page 620
SUMMARY......Page 621
REFERENCES......Page 622
BINDING EXPERIMENTS......Page 624
DISCUSSION......Page 625
REFERENCES......Page 626
89. NO-dependent and NO-independent cGMP synthesis in cortical cholinergic neurons of the rat brain......Page 628
REFERENCES......Page 630
90. Calcium mobilization and cellular contraction of embryonic lens vesicle and neural tube on muscarinic cholinergic stimulation......Page 632
REFERENCES......Page 634
GAIT......Page 636
SEXUAL DYSFUNCTION......Page 637
REFERENCES......Page 638
INTRODUCTION......Page 640
RESULTS AND DISCUSSION......Page 641
REFERENCES......Page 642
93. Transgenic manipulations of neuromuscular junction maintenance......Page 644
REFERENCES......Page 646
94. Tetanic fade is revealed by blocking presynaptic nicotinic receptors containing α3β2 subunits after reducing the safety factor of neuromuscular transmission......Page 648
REFERENCES......Page 650
ISOLATION AND CLONING OF α10......Page 652
ELECTROPHYSIOLOGICAL RECORDINGS......Page 653
RESULTS......Page 654
REFERENCES......Page 656
AChE ASSAYS......Page 658
DISCUSSION......Page 659
REFERENCES......Page 660
REACTION WITH SUBSTRATES......Page 662
KINETICS OF THE REACTION......Page 663
REFERENCES......Page 664
WATER PROPERTIES......Page 666
REFERENCES......Page 667
99. α-Conotoxins PnIA and [A10L]PnIA stabilize different states of the chick neuronal α7 acetylcholine receptor......Page 668
REFERENCES......Page 669
100. Acetylcholinesterase knockout mice have increased sensitivity to scopolamine and atropine......Page 670
REFERENCES......Page 671
101. Investigating the diversity of acetylcholinesterase in insect species......Page 672
REFERENCE......Page 673
RESULTS......Page 674
REFERENCES......Page 675
IMMUNOLOCALIZATION STUDIES......Page 676
REFERENCES......Page 677
RESULTS AND DISCUSSION......Page 678
REFERENCES......Page 681
105. Mapping the acetylcholine-binding sites of Torpedo nicotinic receptor using photoaffinity labeling: past, present, and future......Page 684
REFERENCES......Page 686
RESULTS AND DISCUSSION......Page 688
REFERENCES......Page 689
RESULTS AND DISCUSSION......Page 690
REFERENCES......Page 693
108. Identification and characterization of a diverse family of neurotoxin-like peptides from the South American coral snake......Page 694
AChE−/− MICE ARE RESISTANT TO OXOTREMORINE (OXO)-INDUCED HYPOTHERMIA, TREMOR, SALIVATION, AND ANALGESIA......Page 696
MUSCARINIC RECEPTOR mRNA LEVELS ARE UNCHANGED IN AChE−/− MICE......Page 697
REFERENCES......Page 698
ENZYME EXTRACTION......Page 700
RESULTS......Page 701
DISCUSSION......Page 702
REFERENCES......Page 703
INTRODUCTION......Page 704
EFFECTS OF MUTATIONS ON HI-6-INDUCED REACTIVATION OF OP-INHIBITED MOUSE AChE......Page 705
DISCUSSION......Page 706
REFERENCES......Page 707
GALANTHAMINE INTERACTS WITH THE CATALYTIC AND THE PERIPHERAL ANIONIC SITE OF AChE......Page 708
REFERENCES......Page 709
DIFFERENTIATION OF NEURONS AND NMJs......Page 712
REFERENCES......Page 713
INTRODUCTION......Page 714
RESULTS......Page 715
REFERENCES......Page 717
INTRODUCTION......Page 718
REFERENCES......Page 719
GENERAL CONCLUSIONS......Page 722
REFERENCES......Page 725
RADIAL ARM MAZE......Page 726
REFERENCES......Page 727
IN VITRO METHODS......Page 728
REFERENCES......Page 729
RESULTS......Page 730
REFERENCES......Page 731
120. Fine-tuning modulation of neuronal muscarinic M1 (facilitatory) and M2 (inhibitory) receptor activation by adenosine at the rat neuromuscular junction......Page 732
REFERENCES......Page 733
RESULTS AND DISCUSSION......Page 736
REFERENCES......Page 738
REFERENCES......Page 740
123. Segregation of phosphatidic acid-rich domains in reconstituted acetylcholine receptor membranes......Page 742
ACKNOWLEDGMENT......Page 743
REFERENCES......Page 744
RESULTS......Page 746
REFERENCES......Page 747
RESULTS AND DISCUSSION......Page 750
REFERENCES......Page 751
THE DETECTION OF UNWANTED ChE-BOUND HIDDEN LIGANDS......Page 752
REFERENCES......Page 754
127. Plant cholinesterase activity as a biosensor; cellular models......Page 756
REFERENCES......Page 757
128. Studies on the mechanism of blockade of acetylcholine release by snake presynaptic PLA2 neurotoxins......Page 758
REFERENCES......Page 760
129. Variability of substrate specificity in cholinesterases of vertebrates and invertebrates......Page 762
REFERENCES......Page 763
GLIOTACTIN—THE EXTRACELLULAR DOMAIN......Page 764
GLIOTACTIN—THE CYTOPLASMIC DOMAIN......Page 765
REFERENCES......Page 766
131. Targeting of the vesicular acetylcholine transporter to cholinergic subdivisions in transgenic mice......Page 768
REFERENCES......Page 770
132. Ligand-induced conformational changes in the omega loop of acetylcholinesterase revealed by fluorescence spectroscopy......Page 772
REFERENCES......Page 773
133. ‘Readthrough’ acetylcholinesterase and cholinergic neurotransmission......Page 774
ACKNOWLEDGMENTS......Page 776
REFERENCES......Page 777
RESULTS AND DISCUSSION......Page 778
REFERENCES......Page 780
RESULTS AND DISCUSSION......Page 782
REFERENCES......Page 783
136. Two-hybrid approach to the intracellular function(s) of readthrough acetylcholinesterase......Page 784
REFERENCES......Page 786
AChE DETERMINATION......Page 788
DISCUSSION......Page 789
REFERENCES......Page 790
138. Effects of carbamate insecticides on rat neuronal α4β4 nicotinic receptors and rat brain acetylcholinesterase......Page 792
REFERENCES......Page 793
CHOLINE SENSITIVITY OF CURRENTS AND CALCIUM INFLUX......Page 794
CONCLUSIONS......Page 795
REFERENCES......Page 796
THEORY......Page 798
RESULTS AND DISCUSSION......Page 801
REFERENCES......Page 803
ALTERNATIVE PASSAGES TO THE ACTIVE SITE......Page 804
REFERENCES......Page 805
STRESS......Page 806
REFERENCES......Page 807
143. Probing the binding interface between the nicotinic acetylcholine receptor and a short α-neurotoxin through receptor-biotinyltoxin-streptavidin ternary complexes......Page 808
HupA AND Tac PROTECT NG108-15 CELLS FROM STAU-INDUCED APOPTOSIS......Page 810
THE ANTI-APOPTOTIC EFFECTS OF HupA AND Tac ARE RELATED TO AChE INHIBITION IN APOPTOTIC CELLS......Page 811
MODULATIONS OF Bax AND Bcl-2 PROTEIN EXPRESSION ARE INVOLVED IN THE ANTI-APOPTOTIC EFFECTS OF HupA AND Tac......Page 813
REFERENCES......Page 814
RESULTS......Page 816
REFERENCES......Page 817
STATISTICAL ANALYSIS......Page 818
DISCUSSION......Page 819
REFERENCES......Page 820
RESULTS......Page 822
REFERENCES......Page 823
148. Use of the morphing graphics technique to visualize conformational differences between acetylcholinesterases from different species and inhibitor-induced conformational changes......Page 824
REFERENCES......Page 825
MATERIALS AND METHODS......Page 828
RESULTS......Page 829
DISCUSSION......Page 830
REFERENCES......Page 831
RESULTS AND DISCUSSION......Page 834
ACKNOWLEDGMENT......Page 836
REFERENCES......Page 837
Index......Page 838