Selective neurotoxicity: with 73 tables
Gespeichert in:
| Format: | Buch |
|---|---|
| Sprache: | English |
| Veröffentlicht: |
Berlin u.a.
Springer
1994
|
| Ausgabe: | 2. print. |
| Schriftenreihe: | Springer study edition
|
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | 1. print. 1992 erschienen in: Handbook of experimental pharmacology ; 102 |
| Beschreibung: | XXXI, 874 S. Ill., graph. Darst. |
| ISBN: | 3540578153 0387578153 |
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| 245 | 1 | 0 | |a Selective neurotoxicity |b with 73 tables |c H. Herken ... (eds.) |
| 250 | |a 2. print. | ||
| 264 | 1 | |a Berlin u.a. |b Springer |c 1994 | |
| 300 | |a XXXI, 874 S. |b Ill., graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 490 | 0 | |a Springer study edition | |
| 500 | |a 1. print. 1992 erschienen in: Handbook of experimental pharmacology ; 102 | ||
| 650 | 4 | |a Neurotoxicology | |
| 650 | 0 | 7 | |a Neurotoxizität |0 (DE-588)4123836-9 |2 gnd |9 rswk-swf |
| 689 | 0 | 0 | |a Neurotoxizität |0 (DE-588)4123836-9 |D s |
| 689 | 0 | |5 DE-604 | |
| 700 | 1 | |a Herken, Hans |d 1912-2003 |e Sonstige |0 (DE-588)11883696X |4 oth | |
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Datensatz im Suchindex
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| adam_text |
CONTENTS
CHAPTER
1
CELLULAR
AND
SUBCELLULAR
TARGETS
OF
NEUROTOXINS:
THE
CONCEPT
OF
SELECTIVE
VULNERABILITY
H.G.
B
AUMGARTEN
AND
B.
Z
IMMERMANN
.
WITH
12
FIGURES
.
1
A.
INTRODUCTION
.
1
B.
CENTRAL
GLUTAMATERGIC
AND
ASPARTATERGIC
PATHWAYS
AS
MEDIATORS
OF
EXCITOTOXICITY
.
3
C.
ROLE
OF
ACTIVE
TRANSPORT
SYSTEMS
AS
MEDIATORS
OF
SELECTIVE
NEUROTOXICITY
.
7
D.
THE
CENTRAL
DOPAMINERGIC
SYSTEMS
AS
TARGETS
OF
NEUROTOXINS
.
8
E.
THE
CENTRAL
NORADRENERGIC
SYSTEMS
AS
TARGETS
OF
NEUROTOXINS
.
9
F.
THE
CENTRAL
SEROTONERGIC
SYSTEMS
AS
TARGETS
OF
NEUROTOXINS
.
11
G.
THE
CENTRAL
CHOLINERGIC
SYSTEMS
AS
TARGETS
OF
NEUROTOXINS
.
14
H.
CHOLINOCEPTIVE
MECHANISMS
AS
MEDIATORS
OF
CNS
TOXICITY
.
16
J.
VULNERABILITY
OF
THE
CNS
TO
ANTINIACIN
COMPOUNDS
.
18
K.
VULNERABILITY
OF
THE
CNS
TO
DRUGS AFFECTING
OXIDATION
PHOSPHORYLATION
COUPLING
.
20
L.
VULNERABILITY
OF
NEURONS
DUE
TO
THE
INTERACTION
OF
TOXINS
WITH
THE
CYTOSKELETON
.
20
REFERENCES
.
22
CHAPTER
2
PROTECTIVE
BARRIERS
IN
THE
PERIPHERAL
NERVOUS
SYSTEM
TO
NEUROTOXIC
AGENTS
Y.
O
LSSON
.
WITH
5
FIGURES
.
29
A.
TOXIC
INJURY
AND
PROTECTIVE
BARRIERS
OF
THE
NERVOUS
SYSTEM
.
29
B.
MICROENVIRONMENT
OF
PERIPHERAL
NERVES
.
29
I.
INTRAFASCICULAR
STRUCTURAL
COMPONENTS
.
30
II.
INTRAFASCICULAR
FLUID
.
31
1.
COMPOSITION
.
32
2.
FORMATION
AND
RESORPTION
.
32
3.
INTRAFASCICULAR
FLOW
.
33
XII
CONTENTS
C.
BARRIER
IN
THE
VASA
NERVORUM
OF
PERIPHERAL
NERVES
.
34
I.
BLOOD
SUPPLY
.
34
II.
VASCULAR
PERMEABILITY
.
35
1.
ENDONEURIAL
VESSELS
.
36
2.
EPINEURIAL
VESSELS
.
39
D.
BARRIER
IN
THE
PERINEURIUM
OF
PERIPHERAL
NERVES
.
39
I.
STRUCTURE
.
40
II.
PROPERTIES
.
41
1.
BARRIER
TO
VARIOUS
COMPOUNDS
.
42
2.
SITE
OF
THE
BARRIER
.
43
E.
BARRIERS
IN
PERIPHERAL
GANGLIA
.
44
I.
BLOOD
SUPPLY
.
44
II.
VASCULAR
PERMEABILITY
.
44
III.
EXTRACELLULAR
SPACES
.
45
IV.
CAPSULE
.
46
F.
BARRIERS
AND
TOXIC
LESIONS
OF
THE
PNS
.
47
I.
DIPHTHERIC
NEUROPATHY
.
48
II.
NEUROPATHIES
DUE
TO
METAL
INTOXICATION
.
48
1.
LEAD
INTOXICATION
.
48
2.
MERCURY
INTOXICATION
.
49
3.
CADMIUM
INTOXICATION
.
50
III.
NEUROPATHY
DUE
TO
INDUSTRIAL
AGENTS
.
51
1.
TOXIC
OIL
SYNDROME
.
51
IV.
NEUROPATHY
DUE
TO
DRUGS
.
52
1.
HEXACHLOROPHENE
NEUROPATHY
.
52
2.
ISONIAZID
NEUROPATHY
.
53
3.
DOXORUBICIN
NEUROTOXICITY
.
53
4.
NEUROTOXICITY
OF
LOCAL
ANESTHETICS
.
54
G.
CONCLUDING
REMARKS
.
55
REFERENCES
.
56
CHAPTER
3
PROTECTIVE
BARRIERS
IN
THE
NERVOUS
SYSTEM
AGAINST
NEUROTOXIC
AGENTS:
THE
BLOOD-BRAIN
BARRIER
B.B.
J
OHANSSON
.
WITH
2
FIGURES
.
67
A.
INTRODUCTION
.
67
B.
MORPHOLOGY
OF
BRAIN
ENDOTHELIAL
CELLS
.
67
C.
ENDOTHELIAL
CELL
POLARITY
.
68
D.
POSSIBLE
ROLE
OF
PERIVASCULAR
ASTROCYTES
.
68
E.
PASSAGE
ACROSS
THE
ENDOTHELIAL
CELL
MEMBRANE
.
69
I.
ROLE
OF
LIPID
SOLUBILITY
.
69
1.
HEXACARBONS
.
69
2.
CARBON
DISULFIDE
.
69
CONTENTS
XIII
3.
ORGANOPHOSPHORUS
COMPOUNDS
.
70
4.
METHYL
MERCURY
.
70
5.
TRIETHYLTIN
.
70
II.
TRANSPORT
MECHANISMS
.
70
1.
THE
GLUCOSE
CARRIER
.
70
2.
CARRIERS
FOR
AMINO
ACIDS
.
71
3.
PEPTIDES
.
71
4.
THE
MONOCARBOXYLIC
ACID
TRANSPORTER
.
71
5.
ORGANIC
ACIDS
.
72
6.
ELECTROLYTES
.
72
7.
OTHERS
.
72
F.
ENZYMATIC
BARRIERS
.
72
G.
SPONTANEOUS
AND
INDUCED
FLUCTUATIONS
OF
BLOOD-BRAIN
BARRIER
FUNCTION
.
73
H.
METHODS
TO
FACILITATE
PASSAGE
OF
SUBSTANCES
FROM BLOOD
TO
BRAIN
.
.
74
I.
INCREASING
LIPID
SOLUBILITY
.
74
II.
CATIONIZATION
AND
GLYCOSYLATION
.
75
III.
COUPLING
TO
SUBSTANCES
ENTERING
BY
RECEPTOR-MEDIATED
TRANSPORT
.
75
IV.
LIPOSOME
ENTRAPMENT
.
75
V.
METHODS
TO
OPEN
THE
BLOOD-BRAIN
BARRIER
EXPERIMENTALLY
.
.
75
J.
LONG-TERM
CONSEQUENCES
OF
BLOOD-BRAIN
BARRIER
ALTERATIONS
.
76
K.
SUBSTANCES
THAT
ENTER
THE
BRAIN
BY
PRIMARILY
DAMAGING
THE
BLOOD-BRAIN
BARRIER
.
76
L.
RETROGRADE
INTRAAXONAL
TRANSPORT
IN
MOTOR
NERVES
.
76
M.
AREAS
LACKING
A
BLOOD-BRAIN
BARRIER
.
76
N.
SUMMARY
.
77
REFERENCES
.
77
CHAPTER
4
KINETIC
AND
METABOLIC
DISORDERS
OF
AXOPLASMIC
TRANSPORT
INDUCED
BY
NEUROTOXIC
AGENTS
S.
O
CHS
.
WITH
1
FIGURE
.
81
A.
INTRODUCTION
.
81
B.
THE
TRANSPORT
SYSTEM
81
I.
CHARACTERISTICS
OF
ANTEROGRADE
TRANSPORT
.
81
II.
RETROGRADE
TRANSPORT
AND
TURNAROUND
.
83
III.
TRANSPORT
MODELS
.
84
1.
THE
FAST
TRANSPORT
MECHANISM
.
84
2.
SLOW
TRANSPORT
AND
THE
UNITARY
HYPOTHESIS
.
85
C.
NEUROTOXINS
.
86
I.
CELL
BODY
ACTIONS
.
86
II.
GENERALIZED
ACTIONS
ON
FIBERS
.
87
XIV
CONTENTS
1.
AGENTS
ACTING
ON
THE
AXOLEMMA
.
87
A)
TETRODOTOXIN,
BATRACHOTOXIN
.
87
B)
LOCAL
ANESTHETICS
.
88
2.
METABOLIC
BLOCKERS
.
88
3.
CALCIUM
AND
CALMODULIN
BLOCKING
AGENTS
.
89
4.
TUBULIN-BINDING
AGENTS
.
90
5.
MICROTUBULE
"
STABILIZING
"
AGENTS
.
91
6.
SULFHYDRYL
BLOCKERS
.
91
III.
LOCALIZED
ACTIONS
OF
TOXICANTS
ON
FIBERS
.
92
1.
PROXIMAL
AXONOPATHIES
.
92
A)
P,P'-IMINODIPROPIONITRILE
.
92
B)
ALUMINUM
.
93
2.
DISTAL
AXONOPATHIES
.
94
A)
ACRYLAMIDE
.
94
B)
HEXACARBONS
.
95
C)
P-BROMOPHENYLACETYLUREA
.
96
D)
ZINC
PYRIDINETHIONE
.
97
E)
ORGANOPHOSPHATES
.
97
F)
TULIDORA
(BUCKTHORN)
TOXIN
.
98
G)
ALCOHOL
.
98
D.
CONCLUSIONS
.
99
REFERENCES
.
100
CHAPTER
5
METABOLIC
DISORDERS
AS
CONSEQUENCES
OF
DRUG-INDUCED
ENERGY
DEFICITS
J.
K
RIEGLSTEIN
AND
J.
N
UGLISCH
.
WITH
10
FIGURES
.
ILL
A.
INTRODUCTION
.
ILL
B.
BRAIN
ENERGY
METABOLISM
.
ILL
C.
ENERGY
DEFICITS
.
113
I.
OXYGEN
DEFICIENCY
.
113
II.
SUBSTRATE
DEFICIENCY
.
114
D.
METABOLIC
DISORDERS
AS
CONSEQUENCES
OF
ENERGY
DEFICIT
.
115
I.
CALCIUM
HOMEOSTASIS
.
117
1.
ROUTES
OF
CA
2+
ENTRY
AND MEANS
OF
CA
2+
RELEASE
.
117
2.
DISTURBANCES
OF
NEURONAL
CALCIUM
HOMEOSTASIS
.
120
3.
CALCIUM-RELATED
NEURONAL
DAMAGE
.
121
II.
OXYGEN
RADICALS
.
121
1.
FORMATION
OF
SUPEROXIDE
.
122
A)
MITOCHONDRIA
.
122
B)
OXIDATIVE
ENZYMES
.
123
C)
DEGRADATION
OF
ARACHIDONIC
ACID
AND
OTHER
UNSATURATED
FATTY
ACIDS
.
123
CONTENTS
XV
D)
AUTOXIDATION
.
123
E)
POLYMORPHONUCLEAR
LEUKOCYTES
.
124
2.
FORMATION
OF
HYDROXYL
RADICAL
.
124
3.
BRAIN
DAMAGE
AND
FREE
RADICALS
.
125
E.
DRUG-INDUCED
ENERGY
DEFICITS
.
127
I.
INHIBITORS
OF
OXIDATIVE
PHOSPHORYLATION
.
127
1.
RESPIRATORY
CHAIN
INHIBITORS
.
127
2.
ATP
SYNTHETASE
INHIBITOR
.
129
3.
UNCOUPLERS
.
129
II.
ETHANOL
.
130
III.
CONVULSIVES
.
131
IV.
COMPOUNDS
CAUSING
ENERGY
DEFICITS
BY
ENZYME/MEMBRANE
DEFECTS
.
132
V.
AMMONIA
.
133
F.
CONCLUDING
REMARKS
.
133
REFERENCES
.
134
CHAPTER
6
NEUROTOXIC
SYNTHESIS
BY
ENZYMATIC
ERROR
H.
H
ERKEN
.
WITH
12
FIGURES
.
141
A.
INTRODUCTION
.
141
B.
LETHAL
SYNTHESIS
.
141
I.
TOXICITY
OF
FLUOROACETIC
ACID
.
142
II.
MOLECULAR
BASIS
OF
INTOXICATION
.
142
1.
SYNTHESIS
OF
FLUOROCITRIC
ACID,
INHIBITOR
OF
ACONITASE
.
.
.
144
III.
CITRATE
ACCUMULATION
-
A
MARKER
IN
FLUOROACETATE
INTOXICATION
.
146
C.
BIOSYNTHESIS
OF
NEUROTOXIC
DINUCLEOTIDES
.
147
I.
THE
NAD(P)
GLYCOHYDROLASE-TRANSFERASE
EXCHANGE
REACTION
.
147
II.
3-ACETYLPYRIDINE
AND
3-ACETYLPYRIDINE-ADENINE
DINUCLEOTIDES
.
149
1.
NEUROTOXIC
SYMPTOMS
.
149
2.
MOLECULAR
BASIS
OF
INTOXICATION
.
150
A)
SYNTHESIS
OF
NUCLEOTIDES
CONTAINING
3
ACETYLPYRIDINE
IN
THE
BRAIN
.
150
3.
DISTRIBUTION
OF
3
APADP
IN
THE
BRAIN
REGION
.
151
4.
DYSFUNCTION
OF
OXIDOREDUCTASES
WITH
NUCLEOTIDES
CONTAINING
3
ACETYLPYRIDINE
AS
COENZYME
.
152
5.
PREDILECTION
SITES
OF
FUNCTIONAL
DISORDERS
AND
LESIONS
IN
THE
CENTRAL
NERVOUS
SYSTEM
.
154
6.
METABOLITES
OF
3
ACETYLPYRIDINE
.
156
III.
6
AMINONICOTINAMIDE
AND
6-AMINONICOTINAMIDE-ADENINE
DINUCLEOTIDES
.
157
XVI
CONTENTS
1.
NEUROTOXICITY
.
157
2.
BIOCHEMICAL
BASIS
OF
ACTION
.
158
A)
SYNTHESIS
OF
NUCLEOTIDES
CONTAINING
6-AMINONICOTINAMIDE
BY
NAD(P)
GLYCOHYDROLASE
.
.
.
158
3.
6-ANADP,
INHIBITOR
OF
OXIDOREDUCTASES,
AND
THE
BLOCKADE
OF
THE
HEXOSE
MONOPHOSPHATE
PATHWAY
.
160
4.
INHIBITION
OF
PHOSPHOGLUCOSE
ISOMERASE
BY
PHOSPHOGLUCONATE
.
164
5.
CARBOHYDRATE
METABOLISM
IN
THE
BRAIN
AFTER
INHIBITION
OF
PHOSPHOGLUCOSE
ISOMERASE
.
165
6.
INHIBITION
OF
GLUCOSE
UTILIZATION
IN
THE
GLUTAMATE
Y-AMINOBUTYRIC
ACID
ROUTE
.
169
D.
LESIONS
OF
NEUROGLIA
CELLS
.
170
E.
6-AMINONICOTINAMIDE
INDUCES
A
PARKINSON-LIKE
SYNDROME
.
172
I.
DECREASE
OF
TETRAHYDROBIOPTERIN
CONTENT
AND
DOPA
PRODUCTION
IN
PC
12
CLONAL
CELL
LINE
INDUCED
BY
6-AMINONICOTINAMIDE
.
.
175
II.
DE
NOVO
SYNTHESIS
OF
BIOPTERIN
AND
THE
SALVAGE
PATHWAY
OF
SYNTHESIS
.
177
III.
BIOPTERIN
RECYCLING
PATHWAY
AND
DOPA
PRODUCTION
.
179
REFERENCES
.
180
CHAPTER
7
NEUROTROPIC
CARCINOGENESIS
W.J.
Z
ELLER
.
193
A.
INTRODUCTION
.
193
B.
NEUROTROPIC
CARCINOGENICITY
OF
ALKYLNITROSOUREAS
.
194
I.
ACTIVITY
IN
ADULT
ANIMALS
.
194
1.
METHYLNITROSOUREA,
ETHYLNITROSOUREA
.
194
2.
NEUROTROPIC,
CARCINOGENICITY
OF
ALKYLNITROSOUREAS
WITH
INCREASING
LENGTH
OF
THE
ALKYL
SUBSTITUENT
.
196
II.
TRANSPLACENTAL
AND
PERINATAL
ACTIVITY
OF
ALKYLNITROSOUREAS
.
.
197
1.
TRANSPLACENTAL
ACTIVITY
OF
ETHYLNITROSOUREA
IN
RATS
.
.
.
197
A)
COMPARATIVE
SENSITIVITY
OF
THE
NERVOUS
SYSTEM
TO
ETHYLNITROSOUREA
IN
DIFFERENT
PHASES
OF
DEVELOPMENT:
INTERSPECIES
COMPARISONS
.
197
2.
TRANSPLACENTAL
AND
POSTNATAL
ACTIVITY
OF
FURTHER
COMPOUNDS
OF
THE
HOMOLOGOUS
SERIES
OF
ALKYLNITROSOUREAS
IN
RATS
.
203
III.
DIAGNOSIS
AND
HISTOLOGY
OF
NEUROGENIC
TUMORS
IN
RODENTS
.
203
IV.
NEUROTROPIC
CARCINOGENESIS
IN
NONHUMAN
PRIMATES
.
206
V.
FURTHER
A-NITROSO
COMPOUNDS
.
206
CONTENTS
XVII
VI.
AZO-,
AZOXY-,
AND
HYDRAZO
COMPOUNDS
.
207
VII.
ARYLDIALKYLTRIAZENES
.
208
VIII.
OTHER
ALKYLATING
AGENTS
AND
MISCELLANEOUS
COMPOUNDS
.
.
210
IX.
MECHANISMS
INVOLVED
IN
NEUROONCOGENESIS
.
211
X.
MALIGNANT
TRANSFORMATION
OF
RAT
NEURAL
CELIS
IN
VITRO
AND
IN
VIVO
.
215
REFERENCES
.
217
CHAPTER
8
NEUROTOXIC
PHENYLALKYLAMINES
AND
INDOLEALKYLAMINES
H.G.
B
AUMGARTEN
AND
B.
Z
IMMERMANN
.
WITH
10
FIGURES
.
225
A.
INTRODUCTION
.
225
B.
HYDROXYLATED
ANALOGUES
OF
DOPAMINE
.
226
I.
FALSE
TRANSMITTER
POTENTIAL
OF
6-HYDROXYDOPAMINE
.
226
II.
STRUCTURE-ACTIVITY
RELATIONSHIP
OF
DOPAMINE
ANALOGUES
.
.
.
227
1.
COMPETITION
FOR
CATECHOLAMINE
AND
SEROTONIN
TRANSPORT
SITES
.
227
2.
ACUTE
DISPLACEMENT
OF
[
3
H]NOREPINEPHRINE
BY
HYDROXYLATED
PHENYLETHYLAMINES
.
228
3.
ACUTE
AND
LONG-TERM
DEPLETION
OF
TISSUE
NOREPINEPHRINE
CONTENT
BY
VARIOUS PHENYLETHYLAMINES
.
.
228
4.
LONG-TERM
EFFECTS
OF
TRIHYDROXY
PHENYLETHYLAMINES
ON
THE
UPTAKE
OF
[
3
H]NOREPINEPHRINE
IN
VIVO
.
229
5.
TIME
COURSE
OF
EFFECTS
OF
6-HYDROXYDOPAMINE
ON
(
3
H)NOREPINEPHRINE
UPTAKE
AND
ON
CNS
CATECHOLAMINE
LEVELS
.
229
III.
AUTOXIDATION
AND
CATALYZED
OXIDATION
OF
DOPAMINE
AND
TRIHYDROXYPHENYLETHYLAMINES
.
231
1.
PATHWAYS,
PRODUCTS,
AND
BYPRODUCTS
OF
AUTOXIDATION
.
.
.
232
2.
RADICAL-CATALYZED
OXIDATION
.
233
IV.
EFFECT
OF
RADICAL
SCAVENGERS
ON
THE
AXODESTRUCTIVE
POTENCY
OF
6-HYDROXYDOPAMINE
IN
VIVO
.
237
V.
ROLE
OF
COVALENT
MODIFICATION
OF
PROTEINS
VERSUS
ROLE
OF
FREE
RADICALS
IN
TOXICITY
OF
6-HYDROXYDOPAMINE
.
238
1.
STUDIES
IN
PROTEIN
MODEL
SYSTEMS
.
238
2.
IN
VIVO
STUDIES
.
239
3.
STUDIES
IN
ENZYME
SYSTEMS
.
239
4.
STUDIES
IN
CELL
CULTURE
SYSTEMS
.
241
C.
DSP-4-TARGETS
AND
MECHANISM
OF
ACTION
.
246
D.
HYDROXYLATED
ANALOGUES
OF
TRYPTAMINE
AND
SEROTONIN
.
248
I.
FALSE
TRANSMITTER
POTENTIAL
OF
5,6
AND
5,7-DIHYDROXYTRYPTAMINE
.
248
II.
STRUCTURE-ACTIVITY
RELATIONSHIP
.
249
XVIII
CONTENTS
1.
COMPETITION
FOR
MONOAMINE
UPTAKE
SITES
.
249
2.
IMPAIRMENT
OF
[
3
H]-SEROTONIN
AND
[
3
H]-NOREPINEPHRINE
UPTAKE
.
251
3.
LONG-TERM
EFFECTS
OF
DIHYDROXYTRYPTAMINES
ON
CEREBRAL
MONOAMINE
LEVELS
AND
MORPHOLOGY
OF
SEROTONERGIC
AXONS
.
252
III.
AUTOXIDATION
OF
DIHYDROXYTRYPTAMINES
.
253
1.
PATHWAYS,
PRODUCTS,
BYPRODUCTS,
AND
BIOLOGICAL
CONSEQUENCES
OF
AUTOXIDATION
OF
5,
6-DHT
.
255
2.
PATHWAYS,
PRODUCTS,
BYPRODUCTS,
AND
BIOLOGICAL
CONSEQUENCES
OF
AUTOXIDATION
OF
5,
7-DHT
.
259
A)
KETO-ENOL
TAUTOMERISM
.
259
B)
CHARACTERISTICS,
PRODUCTS,
AND
BIOLOGICAL
CONSEQUENCES
.
259
3.
RELEVANCE
OF
AUTOXIDATION
FOR
NEUROTOXICITY
.
261
IV.
POTENTIAL
INTRACELLULAR
CATALYTIC
MECHANISMS
INVOLVED
IN
ENHANCEMENT
OF
AUTOXIDATION
OF
5,
7-DHT
AND
RADICAL
FORMATION
.
262
E.
SUBSTITUTED
AMPHETAMINES
.
265
I.
NEUROTOXICITY
.
265
II.
IMPORTANCE
OF
PHARMACOKINETICS
AND METABOLISM
IN
THE
LONG-TERM
ACTIONS
OF
FENFLURAMINE
.
267
III.
DO
AMPHETAMINES
CAUSE
ACUTE
DESTRUCTION
OF
SEROTONERGIC
AXONS
LIKE
5,
7-DHT?
.
269
IV.
RELEVANCE
OF
6-HYDROXYDOPAMINE
AND
DIHYDROXYTRYPTAMINE-INDUCED
NEUROTOXICITY
.
270
1.
DRUG-INDUCED
TOXICITY
IN
CENTRAL
MONOAMINERGIC
NEURONS
.
270
2.
MONOAMINE
NEUROTOXINS,
AGING,
AND
DISEASE
.
274
F.
CONCLUSIONS
.
276
REFERENCES
.
279
CHAPTER
9
TOXINS
AFFECTING
THE
CHOLINERGIC
SYSTEM
H.
H
ORTNAGL
AND
I.
H
ANIN
.
WITH
2
FIGURES
.
293
A.
INTRODUCTION
.
293
B.
TARGET
SITES
OF
CHOLINERGIC
TOXINS
AT
VARIOUS
LEVELS
OF
THE
CHOLINERGIC
NEURON
.
294
C.
TOXINS
EFFECTIVE
AT
THE
PERIKARYON
OF
THE
CHOLINERGIC
NEURON
.
.
.
296
D.
TOXINS
EFFECTIVE
AT
THE
LEVEL
OF
THE
CHOLINERGIC
NERVE
TERMINAL
.
.
298
I.
HIGH-AFFINITY
CHOLINE
TRANSPORT
(HACHT)
SYSTEM
.
298
1.
REVERSIBLE
INTERACTIONS
.
298
2.
IRREVERSIBLE
INTERACTIONS
.
300
CONTENTS
XIX
A)
IN
VITRO
STUDIES
.
300
B)
EFFECTS
IN
NEURONAL
TISSUE
CULTURE
SYSTEMS
.
301
C)
IN
VIVO
STUDIES
.
301
D)
STRUCTURAL
REQUIREMENTS
AND
QUESTION
OF
SPECIFICITY
OF
AF64A
.
304
II.
ACETYLCHOLINE
SYNTHESIS,
STORAGE,
AND
RELEASE
.
306
1.
INHIBITION
OF
ACETYLCHOLINE
SYNTHESIS
.
306
2.
INHIBITION
OF
ACETYLCHOLINE
STORAGE
.
307
3.
ACETYLCHOLINE
RELEASE
.
308
III.
OTHER
TOXINS
AT
THE
PRESYNAPTIC
LEVEL
.
309
E.
TOXINS
INTERFERING
AT
THE
LEVEL
OF
THE
SYNAPSE
.
310
F.
NEUROTOXINS
WITH
MISCELLANEOUS
ACTIONS,
PREFERENTIALLY
AFFECTING
CHOLINERGIC
PATHWAYS
.
313
I.
COLCHICINE
.
313
II.
ETHANOL
.
315
III.
ALUMINUM
.
316
G.
CONCLUDING
REMARKS
.
317
REFERENCES
.
318
CHAPTER
10
MECHANISMS
OF
L-METHYL-4-PHENYL-L,2,3,6-TETRAHYDROPYRIDINE
INDUCED
DESTRUCTION
OF
DOPAMINERGIC
NEURONS
I.J.
K
OPIN
.
WITH
1
FIGURE
.
333
A.
INTRODUCTION
.
333
B.
BIOACTIVATION
OF
MPTP
TO
MPP
+
BY
MONOAMINE
OXIDASE
.
334
C.
TOXICITY
OF
MPTP
ANALOGUES
.
335
D.
ALTERNATIVE
ROUTES
FOR
MPTP
METABOLISM
.
337
E.
MECHANISM
OF
MPTP
ACTIVATION
BY
MONOAMINE
OXIDASE
.
338
I.
INHIBITION
OF
MONOAMINE
OXIDASE
BY
MPTP
.
338
II.
CELLULAR
LOCALIZATION
OF
MONOAMINE
OXIDASES
.
339
III.
UPTAKE
OF
MPP
+
.
341
F.
MOLECULAR
BASES
FOR
MPP
+
TOXICITY
.
342
I.
INHIBITION
OF
MITOCHONDRIAL
RESPIRATION
BY
MPP
+
.
344
G.
ROLE
OF
NEUROMELANIN
IN
MPTP
TOXICITY
.
347
H.
CONCLUSION
.
348
REFERENCES
.
349
CHAPTER
11
TETANUS
AND
BOTULINUM
NEUROTOXINS
H.H.
W
ELLHONER
.
WITH
1
FIGURE
.
357
A.
INTRODUCTION
.
357
B.
SOURCES
OF
CLOSTRIDIAL
NEUROTOXINS
.
358
XX
CONTENTS
C.
PRODUCTION,
PURIFICATION,
AND
STRUCTURE
.
358
I.
INTRODUCTION
.
358
II.
TERMINOLOGY
OF
THE
TOXIN
FRAGMENTS
.
359
III.
PRODUCTION
AND
PURIFICATION
.
360
IV.
PRIMARY
STRUCTURES
.
361
1.
TETANUS
TOXIN
.
361
2.
BOTULINUM
A
TOXIN
.
362
3.
BOTULINUM
B
TOXIN
.
363
4.
BOTULINUM
CL
TOXIN
.
363
5.
BOTULINUM
D
TOXIN
.
363
6.
BOTULINUM
E
TOXIN
.
363
V.
HIGHER
STRUCTURES
.
363
1.
CRYSTALLOGRAPHY
.
363
2.
SECONDARY
STRUCTURE
.
364
3.
TERTIARY
STRUCTURE
.
364
VI.
BINDING,
UPTAKE,
ROUTING,
AND
ACTION
OF
CLOSTRIDIAL
NEUROTOXINS
AS
A
FUNCTION
OF
THEIR
SUBUNITS
AND
STRUCTURE
.
.
.
365
1.
INTRODUCTION
.
365
2.
ISOTOXINS AND SUBUNITS
OF
THE
CLOSTRIDIAL
NEUROTOXINS
.
.
.
365
A)
NICKING
.
365
B)
FUNCTION
OF
THE
L-CHAIN
.
366
C)
FUNCTION
OF
THE
H-CHAIN
.
366
D)
FUNCTIONS
ASSIGNED
TO
THE
C-TERMINAL
PART
OF
THE
H-CHAIN,
H
C
.
367
E)
FUNCTIONS
ASSIGNED
TO
THE
N-TERMINAL
PART
OF
THE
H-CHAIN
.
367
F)
INTERACTION
OF
THE
L-CHAIN
WITH
THE
H-CHAIN,
H
N
.
367
G)
THE
L-CHAIN
LINKED
TO
THE
C-TERMINAL
PART
OF
THE
H-CHAIN,
L-H
N
.
367
3.
MODIFICATION
OF
AMINO
ACIDS
.
368
D.
BINDING
OF
CLOSTRIDIAL
NEUROTOXINS
TO
CELLS
AND
THE
ROUTING
OF
THE
TOXINS
THROUGH
NEURONS
.
370
I.
THE
THREE-STEP
MODEL
.
370
II.
BINDING
.
371
1.
CELL
SPECIFICITY
.
371
2.
AFFINITY
OF
BINDING
.
373
3.
CHEMICAL
NATURE
OF
THE
BINDING
SITES
.
373
III.
UPTAKE
OF
CLOSTRIDIAL
NEUROTOXINS
INTO
ENDOSOMES
OF
NEURONS
.
376
IV.
HANDLING
OF
THE
CLOSTRIDIAL
NEUROTOXINS
IN
THE
ENDOSOMES
.
377
V.
AXONAL
TRANSPORT
.
378
VI.
ELIMINATION
AND
DEGRADATION
.
379
VIL
TRANSSYNAPTIC
TRANSPORT
.
380
CONTENTS
XXI
E.
ACTIONS
OF
CLOSTRIDIAL
NEUROTOXINS
.
380
I.
INTRODUCTION
.
380
II.
THE
LOCUS
AND
THE
PHENOMENOLOGY
OF
ACTION
.
381
1.
CLOSTRIDIAL
NEUROTOXINS
DO
NOT
IMPAIR
CONDUCTION
.
381
2.
ION
FLUXES
THROUGH
THE
PLASMA
MEMBRANES
OF
PRESYNAPTIC
TERMINALS
.
381
A)
ACTION
ON
CALCIUM
FLUXES
THROUGH
NEURONAL
PLASMA
MEMBRANES
.
381
B)
INFLUENCE
OF
ELEVATED
EXTRACELLULAR
CA
2+
CONCENTRATION,
OF
OTHER
CATIONS,
AND
OF
AMINOPYRIDINES
.
382
3.
ACTIONS
ON
THE
SYNTHESIS,
REUPTAKE,
REPARTITION,
AND
STORAGE
OF
TRANSMITTERS
.
383
A)
SYNTHESIS
.
383
B)
UPTAKE
.
383
C)
CONTENT
.
383
D)
COMPARTMENTALIZATION
.
384
4.
CLOSTRIDIAL
NEUROTOXINS
IMPAIR
THE
RELEASE
OF
TRANSMITTERS,
NEUROHOROMONES,
AND
NEUROMODULATORS
.
.
384
A)
BIOCHEMICAL
AND
BIOPHYSICAL
EVIDENCE
.
384
B)
QUANTITATIVE
COMPARISONS
.
389
5.
ACTION
ON
POSTSYNAPTIC
CELLS
.
391
6.
LATE
EFFECTS
.
391
A)
DAMAGE
TO
NEURONS
.
391
B)
SPROUTING
.
391
C)
LARGE-SIZED
MEPPS
.
392
7.
ACTION
ON
NONNEURONAL
CELLS
.
392
8.
ACTION
ON
MULTICELLULAR
SYSTEMS
.
392
A)
NEURONAL
SYSTEMS
.
392
B)
NONNEURONAL
SYSTEMS
.
392
III.
INTRACELLULAR
MODE
OF
ACTION
.
393
G.
ANTIBODIES
AGAINST
CLOSTRIDIAL
NEUROTOXINS
AS
EXPERIMENTAL
TOOLS
.
394
I.
MONOCLONAL
ANTIBODIES
.
394
II.
NEUTRALIZATION
OF
CELL-ASSOCIATED
CLOSTRIDIAL
NEUROTOXINS
WITH
ANTIBODIES
.
395
REFERENCES
.
396
CHAPTER
12
CAPSAICIN:
SELECTIVE
TOXICITY
FOR
THIN
PRIMARY
SENSORY
NEURONS
P.
H
OLZER
.
WITH
1
FIGURE
.
419
A.
INTRODUCTION
.
419
B.
TYPES
AND
TARGETS
OF
ACTION
.
420
I.
TYPES
OF
PRIMARY
AFFERENT
NEURONS
.
420
II.
ACUTE
EXICTATORY
EFFECTS
ON
SENSORY
NEURONS
.
421
XXII
CONTENTS
1.
TARGETS
OF
ACTION
.
421
2.
CONSEQUENCES
OF
EXCITATION
.
424
III.
INTERMEDIATE
EFFECTS
ON
SENSORY
NEURONS
.
425
1.
SENSITIZATION
AND
DESENSITIZATION
.
425
2.
BLOCKADE
OF
NERVE
CONDUCTION
.
426
IV.
NEUROTOXIC
EFFECTS
ON
MAMMALIAN
SENSORY
NEURONS
.
427
1.
EFFECTS
OF
SYSTEMIC
TREATMENT
IN
NEWBORN
MAMMALS
.
.
.
427
A)
RAT
.
427
B)
OTHER
MAMMALS
.
432
2.
EFFECTS
OF
SYSTEMIC
TREATMENT
IN
ADULT
MAMMALS
.
433
A)
RAT
.
433
B)
GUINEA-PIG
.
436
C)
OTHER
MAMMALS
.
437
3.
EFFECTS
OF
PERIAXONAL
APPLICATION
.
438
A)
RAT
.
438
B)
OTHER
MAMMALS
.
439
4.
EFFECTS
OF
LOCAL
APPLICATION
.
440
A)
INTRATHECAL
OR
INTRACISTERNAL
ADMINISTRATION
.
440
B)
INTRACEREBROVENTRICULAR
ADMINISTRATION
.
441
C)
TOPICAL
ADMINISTRATION
TO
SPECIFIC
BRAIN
REGIONS
.
441
D)
TOPICAL
ADMINISTRATION
TO
PERIPHERAL
ENDINGS
OF
SENSORY
NEURONS
.
441
5.
EFFECTS
ON
SENSORY
NEURONS
IN
VITRO
.
442
6.
EFFECTS
ON
SENSORY
NEURONS
IN
CULTURE
.
443
7.
AGE,
STRAIN,
AND
SPECIES
DIFFERENCES
IN
SENSITIVITY
.
444
V.
ACUTE
AND
LONG-TERM
EFFECTS
IN
NONMAMMALIAN
SPECIES
.
.
.
445
VI.
SUMMARY
.
446
1.
CAPSAICIN-SENSITIVE
NEURONS
.
446
2.
NEURONS
NOT
SENSITIVE
TO
CAPSAICIN
.
447
C.
MECHANISMS
OF
ACTION
.
448
I.
STRUCTURE-ACTIVITY
RELATIONSHIPS
.
448
II.
EFFECTS
ON
THE
CELL
MEMBRANE
.
451
1.
SENSORY
NEURON-SELECTIVE
EFFECTS
.
451
2.
CELL-NONSELECTIVE
EFFECTS
.
452
III.
INTRACELLULAR
EFFECTS
.
453
1.
ION
ACCUMULATION,
PEPTIDE
RELEASE,
AND
BIOCHEMICAL
EFFECTS
.
453
2.
NONSPECIFIC
DESENSITIZATION
.
454
3.
NEUROTOXICITY
.
455
IV.
RUTHENIUM
RED
AS
A
CAPSAICIN
ANTAGONIST
.
456
V.
INTERACTION
WITH
NERVE
GROWTH
FACTOR
.
457
VI.
SITES
OF
ACTION
ON
SENSORY
NEURONS
.
457
VIL
SUMMARY
.
458
D.
CAPSAICIN
AS
A
PHARMACOLOGICAL
TOOL
.
459
REFERENCES
.
460
CONTENTS
XXIII
CHAPTER
13
EXCITOTOXINS,
GLUTAMATE
RECEPTORS,
AND
EXCITOTOXICITY
V.I.
T
EICHBERG
.
483
A.
INTRODUCTION
.
483
B.
EXCITOTOXINS
AND
EXCITOTOXICITY
.
483
C.
EXCITOTOXINS
AND
GLUTAMATE
RECEPTORS
.
483
I.
THE
A-METHYL-D-ASPARTATE
RECEPTOR
.
484
1.
PHARMACOLOGICAL
AND
ELECTROPHYSIOLOGICAL
CHARACTERIZATION
.
484
2.
BIOCHEMICAL
AND
STRUCTURAL
CHARACTERIZATION
.
486
II.
THE
KAINATE
RECEPTOR
.
487
1.
PHARMACOLOGICAL
AND
ELECTROPHYSIOLOGICAL
CHARACTERIZATION
.
487
2.
BIOCHEMICAL
AND
STRUCTURAL
CHARACTERIZATION
.
489
III.
THE
A-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLEPROPIONATE
RECEPTOR
.
491
1.
PHARMACOLOGICAL
AND
ELECTROPHYSIOLOGICAL
CHARACTERIZATION
.
491
2.
BIOCHEMICAL
AND
STRUCTURAL
CHARACTERIZATION
.
491
IV.
THE
2-AMINO-4-PHOSPHONOBUTYRATE
RECEPTOR
.
492
V.
THE
7RANS-L-AMINO-L,3-CYCLOPENTANEDICARBOXYLATE
RECEPTOR
.
492
1.
PHARMACOLOGICAL
AND
ELECTROPHYSIOLOGICAL
CHARACTERIZATION
.
492
D.
MECHANISMS
OF
ACTION
OF
EXCITOTOXIC
SUBSTANCES
.
493
I.
A-METHYL-D-ASPARTATE-INDUCED
EXCITOTOXICITY
.
494
1.
EARLY
EVENTS:
ROLE
OF
SODIUM/CHLORIDE
IONS
.
494
2.
LATE
EVENTS:
ROLE
OF
CALCIUM
IONS
AND
"
DOWNSTREAM
PROCESSES
"
.
495
A)
PERTURBATION
OF
CYTOSKELETAL
ORGANIZATION
.
495
B)
PHOSPHOLIPASE
ACTIVATION
.
496
C)
ENDONUCLEASE
ACTIVATION
.
496
D)
PROTEIN
KINASE
C
ACTIVATION
.
496
E)
XANTHINE
OXIDASE
ACTIVATION
.
497
II.
KAINATE
AND
QUISQUALATE-INDUCED
EXCITOTOXICITY
.
497
E.
ENDOGENOUS
MECHANISMS
OF
PROTECTION
FROM
EXCITOTOXICITY
.
498
I.
RECEPTOR
DESENSITIZATION
.
499
II.
CELLULAR
UPTAKE
OF
GLUTAMATE
.
499
III.
CALCIUM
HOMEOSTASIS
.
499
IV.
BUILT-IN
MECHANISMS
.
499
F.
MECHANISMS
CONTRIBUTING
TO
EXCITOTOXICITY
.
500
I.
ROLE
OF
AFFERENCES
.
500
II.
CELLULAR
METABOLISM
.
500
G.
EXCITOTOXICOLOGY:
NEW
PERSPECTIVES
.
500
REFERENCES
.
500
XXIV
CONTENTS
CHAPTER
14
CONVULSANTS
AND
GAMMA-AMINOBUTYRIC
ACID
RECEPTORS
S.C.R.
L
UMMIS
AND
LL.
M
ARTIN
.
WITH
8
FIGURES
.
507
A.
INTRODUCTION
.
507
B.
PHARMACOLOGY
AND
STRUCTURE
OF
THE
GAB
A
A
RECEPTOR
.
508
C.
COMPETITIVE
ANTAGONISTS
AT
THE
GAB
A
A
RECEPTOR
.
511
D.
CONVULSANT
AGENTS
ACTING
THROUGH
THE
PICROTOXIN/CONVULSANT
RECOGNITION
SITE
.
514
E.
CONVULSANT
AGENTS
ACTING
THROUGH
THE
BENZODIAZEPINE
RECOGNITION
SITE
.
522
F.
CONCLUSIONS
.
526
REFERENCES
.
527
CHAPTER
15
CONVULSANTS
ACTING
AT
THE
INHIBITORY
GLYCINE
RECEPTOR
C.-M.
B
ECKER
.
WITH
6
FIGURES
.
539
A.
THE
GLYCINERGIC
SYSTEM
OF
THE
MAMMALIAN
CENTRAL
NERVOUS
SYSTEM
.
539
I.
POSTSYNAPTIC
RECEPTORS
.
539
II.
GLYCINE
RECEPTORS
AND
CONVULSANTS
.
540
B.
TOXICOLOGY:
STRYCHNINE
AS
A
PROTOTYPIC
GLYCINE
RECEPTOR
ANTAGONIST
.
540
I.
SYMPTOMS
OF
STRYCHNINE
INTOXICATION
.
540
II.
STRYCHNINE
'
S
EFFECT
ON
MOTOR
REGULATION
AND
THE
SOMATOSENSORY
SYSTEM
.
541
III.
AUDITION
AND
VISION
.
542
IV.
OTHER
CENTRAL
NERVOUS
SYSTEM
FUNCTIONS
.
543
C.
THE
INHIBITORY
GLYCINE
RECEPTOR
.
545
I.
RECEPTOR
STRUCTURE
AND
ISOFORMS
.
545
II.
LIGAND
BINDING
DOMAINS
.
548
III.
INTERACTION
OF
LIGAND
BINDING
DOMAINS
.
550
IV.
ION
EFFECTS
ON
LIGAND
BINDING
.
552
D.
GLYCINE
RECEPTOR
PHARMACOLOGY
.
553
I.
AGONIST PHARMACOLOGY
OF
THE
GLYCINE
RECEPTOR
.
553
II.
STRYCHNINE,
DERIVATIVES,
AND
ANALOGUES
.
555
1.
STRUCTURE-ACTIVITY,
RELATIONSHIP
OF
STRYCHNINE-LIKE
ALKALOIDS
.
555
2.
SYNTHETIC
FRAGMENTS
OF
STRYCHNINE:
0-SPIROPYR
ROLDINOINDOLINES
.
557
III.
NONSTRYCHNINE
CONVULSANTS
AS
GYLCINE
RECEPTOR
LIGANDS
.
.
.
558
1.
SYNTHETIC
GLYCINE
RECEPTOR
ANTAGONISTS
.
558
2.
ALKALOID
ANTAGONISTS
AND
OPIOIDS
.
558
IV.
NONSELECTIVE
GABA
A
RECEPTOR
LIGANDS
.
560
CONTENTS
XXV
1.
MUSCIMOL
ANALOGUES
.
560
2.
LIGANDS
OF
THE
GABA
A
RECEPTOR
MODULATORY
DOMAIN
.
.
.
562
3.
AVERMECTIN
B
LA
.
563
4.
CONVULSANT
STEROIDS
.
563
5.
CHANNEL
BLOCKERS
.
564
V.
VARIOUS
EFFECTS
ON
GLYCINE
RECEPTOR
FUNCTION
.
565
E.
CONCLUSIONS
AND
PERSPECTIVES
.
565
REFERENCES
.
565
CHAPTER
16
PEPTIDE
TOXINS
ACTING
ON
THE
NICOTINIC
ACETYLCHOLINE
RECEPTOR
F.
H
UCHO
.
WITH
6
FIGURES
.
577
A.
INTRODUCTION
.
577
I.
TOXINS
AS
TOOLS
IN
NEUROCHEMICAL
RESEARCH
.
577
II.
TOXINS
VS.
ANTIBODIES
.
578
B.
SCOPE
.
578
C.
THE
BIOCHEMISTRY
OF
THE
ACETYLCHOLINE
RECEPTOR
.
579
I.
ASSAY
AND
ISOLATION
.
579
II.
STRUCTURE
.
579
1.
PRIMARY
AND
QUATERNARY
STRUCTURES
.
579
2.
POSTTRANSLATIONAL
MODIFICATIONS
.
580
3.
SECONDARY
STRUCTURE
.
582
4.
NEURONAL
ACETYLCHOLINE
RECEPTORS
AND
BRAIN
A-BUNGAROTOXIN
BINDING
PROTEIN
.
583
III.
FUNCTION
.
583
D.
A-NEUROTOXINS
FROM SNAKE
VENOMS
.
585
I.
GENERAL
PROPERTIES
AND
CLASSIFICATION
.
585
II.
PRIMARY
STRUCTURE
.
588
III.
TERTIARY
STRUCTURE
.
589
IV.
FUNCTIONAL
DOMAIN
.
591
V.
BINDING
DOMAIN
ON
THE
ACETYLCHOLINE
RECEPTOR
.
593
1.
QUATERNARY
STRUCTURE
.
593
2.
PRIMARY
STRUCTURE
.
594
E.
OTHER
PEPTIDE
NEUROTOXINS
.
597
F.
CONCLUSIONS
AND
OUTLOOK
.
598
REFERENCES
.
598
CHAPTER
17
NICOTINIC
ACETYLCHOLINE
RECEPTORS
AND
LOW
MOLECULAR
WEIGHT
TOXINS
K.L.
S
WANSON
AND
E.X.
A
LBUQUERQUE
.
WITH
15
FIGURES
.
611
A.
INTRODUCTION
.
611
B.
NICOTINIC
ACETYLCHOLINE
RECEPTOR
ION
CHANNEL
MACROMOLECULES
.
.
612
XXVI
CONTENTS
C.
TOXINS
AFFECTING
THE
ACH
RECOGNITION
SITE
FOR
CHANNEL
ACTIVATION
.
615
I.
SULFHYDRYL
MODIFICATION
OF
THE
ACH
TARGET
.
615
II.
AGONISTS
.
618
III.
ANTAGONISTS
.
624
D.
ALLOSTERIC
AGONIST
SITES
.
627
E.
ALLOSTERIC
ANTAGONIST
TOXIN
BINDING
SITES
.
628
I.
ELECTROPHYSIOLOGICAL
CHARACTERISTICS
OF
ALLOSTERIC
TOXIN
ACTIONS
.
631
1.
OPEN
CHANNEL
BLOCKADE:
AGONIST
AND
VOLTAGE
DEPENDENCE
.
631
2.
CLOSED
CHANNEL
BLOCKADE:
VOLTAGE
DEPENDENCE
OR
VOLTAGE
AND
TIME
DEPENDENCE
.
635
3.
DESENSITIZATION:
AGONIST
AND
TIME
DEPENDENCE
.
637
II.
ANTAGONIST
ACTIONS
AT
HOMOLOGOUS
RECEPTORS
.
641
III.
STRUCTURE-ACTIVITY
RELATIONSHIPS
AT
ALLOSTERIC
ANTAGONIST
SITES
.
642
F.
POISONING
BY
ANTICHOLINESTERASE
AGENTS
AND
ANTIDOTAL
THERAPY
MEDIATED
BY
ACHR
ACTIONS
.
644
G.
CONCLUSIONS
.
647
REFERENCES
.
648
CHAPTER
18
NEUROTOXIC
AGENTS
INTERACTING
WITH
THE
MUSCARINIC
ACETYLCHOLINE
RECEPTOR
J.
J
ARV
.
WITH
2
FIGURES
.
659
A.
INTRODUCTION
.
659
B.
TOXICANTS
ACTING
ON
THE
MUSCARINIC
RECEPTOR
.
660
I.
AGONISTS AND
ANTAGONISTS
.
660
II.
PARTIAL
AGONISTS
.
661
III.
SNAKE
VENOM
TOXINS
.
661
C.
MECHANISM
OF
ANTAGONIST
INTERACTION
.
662
I.
MUSCARINIC
ANTAGONISTS
AS
RADIOLIGANDS
.
662
II.
KINETIC
STUDIES
WITH
RADIOACTIVE
ANTAGONISTS
.
663
III.
KINETIC
STUDIES
WITH
NONRADIOACTIVE
LIGANDS
.
665
IV.
SUBTYPES
OF
MUSCARINIC
ANTAGONISTS
.
667
D.
MECHANISM
OF
AGONIST
INTERACTION
.
668
I.
AGONIST-ANTAGONIST
COMPETITION
STUDIES
.
668
II.
BINDING
STUDIES
WITH
RADIOACTIVE
AGONISTS
.
669
III.
KINETIC
STUDIES
ON
AGONIST-ANTAGONIST
COMPETITION
.
670
E.
STRUCTURE
OF
MUSCARINIC
NEUROTOXIC
AGENTS
.
670
I.
AGONISTS
AND
ANTAGONISTS:
QUALITATIVE
ASPECTS
.
670
II.
AGONISTS
AND
ANTAGONISTS:
QUANTITATIVE
ASPECTS
.
673
CONTENTS
XXVII
F.
TWO-SITE
MODEL
OF
THE
MUSCARINIC
RECEPTOR
.
675
G.
CONCLUSIONS
.
676
REFERENCES
.
676
CHAPTER
19
PEPTIDE
TOXINS
THAT
ALTER
NEUROTRANSMITTER
RELEASE
J.O.
D
OLLY
.
WITH
10
FIGURES
.
681
A.
INTRODUCTION
.
681
B.
TOXINS
THAT
FACILITATE
INDIRECTLY
THE
NEURONAL
RELEASE
OF
TRANSMITTERS
BY
BLOCKING
K
+
CHANNELS
.
684
I.
DENDROTOXINS
.
684
1.
EFFECTS
IN
THE
PERIPHERAL
NERVOUS
SYSTEM
.
684
2.
ACTIONS
OF
A-DENDROTOXIN
AND
ITS
HOMOLOGUES
IN
THE
CENTRAL
NERVOUS
SYSTEM
.
686
A)
NEUROPHYSIOLOGICAL
DEMONSTRATION
OF
TOXIN-INDUCED
INCREASED
NEURONAL
EXCITABILITY,
FACILITATED
RELEASE
OF
TRANSMITTERS
AND
BLOCKADE
OF
AN
I
A
-LIKE
K
+
CURRENT
.
.
686
B)
DENDROTOXINS
ELICIT
RESTING
EFFLUX
OF
TRANSMITTERS
FROM
SYNAPTOSOMES
AND
ELEVATE
CYTOSOLIC
CA
2+
CONCENTRATION
.
687
II.
NOXIUSTOXIN
AND
CHARYBDOTOXIN
.
689
C.
POLYPEPTIDE
TOXINS
WITH
MULTIPLE
EFFECTS
ON
THE NEURONAL
RELEASE
OF
TRANSMITTERS
.
691
I.
P-BUNGAROTOXIN
AND
RELATED
PHOSPHOLIPASE
A
2
-CONTAINING
TOXINS
.
691
1.
GENERAL
PROPERTIES
OF
P-BUNGAROTOXIN,
NOTEXIN,
CROTOXIN,
AND
TAIPOXIN
.
691
2.
TRIPHASIC
EFFECTS
OF
PHOSPHOLIPASE
A
2
TOXINS
ON
ACETYLCHOLINE
RELEASE:
IMPORTANCE
OF
THE
BLOCKADE
OF
A
PRESYNAPTIC
K
+
CURRENT
.
691
3.
INSIGHTS
INTO
THE
ACTION
OF
P-BUNGAROTOXIN
GAINED
FROM
STUDIES
ON
CENTRAL
NEURONAL
PREPARATIONS
.
693
A)
ELECTROPHYSIOLOGICAL
RECORDINGS
IN
BRAIN
SLICES
SHOWING
THAT
P-BUNGAROTOXIN
PREFERENTIALLY
BLOCKS
TRANSMITTER
RELEASE
.
693
B)
BIOCHEMICAL
EVIDENCE
FOR
ACCEPTOR
BINDING
UNDERLYING
THE
PREFERENTIAL
ACTION
OF
P-BUNGAROTOXIN
ON
NERVE
TERMINALS
.
694
II.
A-LATROTOXIN
.
695
D.
BOTULINUM
NEUROTOXINS
AND
TETANUS
TOXIN:
UNIQUE
PROBES
FOR
STUDYING
NEUROTRANSMITTER
RELEASE
.
696
I.
CLOSTRIDIAL
PROTEINS
THAT
BLOCK
CA
2+
-DEPENDENT
SECRETION
BY
ANALOGOUS
MULTI-STEP
MECHANISMS
.
696
XXVIII
CONTENTS
1.
STRUCTURAL
FEATURES
COMMON
TO
BOTULINUM
NEUROTOXINS
AND
TETANUS
TOXIN
.
697
2.
EXPERIMENTAL
SUPPORT
FOR
TRIPHASIC
MECHANISMS
OF
TOXIN
ACTION
.
697
3.
SUBTILE
DIFFERENCES
IN
THE
PHARMACOLOGICAL
EFFECTS
OF
BOTULINUM
NEUROTOXIN
TYPES
A
AND
B
.
699
II.
CONCLUSIVE
EVIDENCE
THAT
BOTULINUM
NEUROTOXINS
ACT
INTRACELLULARLY
TO
BLOCK
CA
2+
-DEPENDENT
RELEASE
OF
TRANSMITTERS
FROM
VARIOUS
NEURONS
AND
EXOCRINE
CELLS
.
699
III.
LIGHT
CHAIN
OF
BOTULINUM
NEUROTOXIN
BLOCKS
CA
2+
-DEPENDENT
SECRETION
WHEN
APPLIED
INSIDE
MOTOR
NERVE ENDINGS
AND
OTHER
MAMMALIAN
CELLS:
A
VESTIGIAL
INTRACELLULAR
ROLE
FOR
ITS
HEAVY
CHAIN
.
701
IV.
OPTIMAL
TARGETTING/INTERNALISATION
OF
BOTULINUM
NEUROTOXIN
AT
MAMMALIAN
NERVE
TERMINALS
REQUIRES
THE
INTACT
DI-CHAIN
FORM:
FUNCTIONAL
DOMAINS
IN
THE
HEAVY
CHAIN
.
.
.
703
V.
ACTIVITIES
OF
HYBRID
MIXTURES
OF
THE
CHAINS
OF
BOTULINUM
NEUROTOXINS
AND
TETANUS
TOXIN:
BINDING
VIA
THE
HEAVY
CHAIN
TO
DISTINCT
ECTO-ACCEPTORS
UNDERLIES
THEIR
NEURONAL
SPECIFICITIES
.
704
VI.
CLUES
TO
THE
MOLECULAR
BASIS
OF
THE
INTRACELLULAR
ACTION
OF
BOTULINUM
NEUROTOXIN
.
706
REFERENCES
.
710
CHAPTER
20
SODIUM
CHANNEL
SPECIFIC
NEUROTOXINS:
RECENT
ADVANCES
IN
THE
UNDERSTANDING
OF
THEIR
MOLECULAR
MECHANISM
S.
B
ECKER
AND
R.D.
G
ORDON
.
WITH
2
FIGURES
.
719
A.
INTRODUCTION
.
719
B
.
CURRENT
STATUS
OF
THE
MOLECULAR
STRUCTURE
OF
THE
SODIUM
CHANNEL
.
719
C.
DESCRIPTION
OF
TOXINS
BY
CLASS
.
723
I.
TOXINS
THAT
INHIBIT
SODIUM
TRANSPORT
.
723
1.
HETEROCYCLIC
GUANIDINES
.
723
2.
P-CONOTOXINS
.
724
II.
LIPID-SOLUBLE
TOXIC
ACTIVATORS
OF
THE
SODIUM
CHANNEL
.
727
1.
BATRACHOTOXIN
.
727
III.
NORTH
AFRICAN
A-SCORPION
AND
SEA
ANEMONE
TOXINS
.
728
1.
A-SCORPION
TOXINS
.
728
2.
SEA
ANEMONE
TOXINS
.
730
IV.
AMERICAN
P-SCORPION
TOXINS
.
731
V.
OTHER
TOXINS
.
732
CONTENTS
XXIX
1.
CIGUATOXIN
.
732
2.
BREVETOXIN
.
733
D.
CONCLUSIONS
.
733
REFERENCES
.
733
CHAPTER
21
POTASSIUM
CHANNEL
TOXINS
H.
M
EVES
.
WITH
6
FIGURES
.
.
.
.
739
A.
INTRODUCTION
.
739
B.
CHEMISTRY
.
739
C.
BINDING
STUDIES
.
741
D.
CROSS-LINKING
EXPERIMENTS
.
748
E.
SOLUBILIZED
AND
PURIFIED
BINDING
PROTEIN
.
748
F.
ELECTROPHYSIOLOGICAL
EXPERIMENTS
.
751
I.
APAMIN
.
751
II.
CHARYBDOTOXIN,
LEIUROTOXIN,
AND
IBERIOTOXIN
.
753
III.
NOXIUSTOXIN
AND
OTHER
SCORPION
TOXINS
.
756
IV.
DENDROTOXIN,
MAST
CELL
DEGRANULATING
PEPTIDE,
P-BUNGAROTOXIN
.
757
V.
OTHER
TOXINS
.
761
G.
THE
PRESUMED
SITE
OF
ACTION
.
761
REFERENCES
.
765
CHAPTER
22
CALCIUM
CHANNEL
TOXINS
J.
S
TRIESSNIG
AND
H.
G
LOSSMANN
.
WITH
1
FIGURE
.
775
A.
INTRODUCTION
.
775
B.
CALCIUM
CHANNEL
TOXINS
FROM
VENOMOUS
SNAILS:
W-CONOTOXINS.
.
.
776
I.
CO-CONOTOXIN
GVIA
IS
A
SELECTIVE
BLOCKER
OF
N-TYPE,
DIHYDROPYRIDINE-INSENSITIVE
CALCIUM
CHANNELS
.
779
II.
CO-CONOTOXIN
GVIA
REVEALS
FUNCTIONAL
ASSOCIATIONS
BETWEEN
EXCITATORY
AMINO
ACID
RECEPTORS
AND
NEURONAL
CALCIUM
CHANNELS
.
788
III.
PROBING
THE
STRUCTURE
AND
LOCATION
OF
N-TYPE
CALCIUM
CHANNELS
WITH
W-CONOTOXIN
GVIA
DERIVATIVES
.
790
C.
CALCIUM
CHANNEL
TOXINS
FROM
SPIDER
VENOMS
.
792
I.
PEPTIDE
TOXINS
.
792
1.
W-AGATOXINS
.
792
2.
HOLOLENA
CURTA
TOXINS
.
793
3.
PLECTREURYS
TRISTES
TOXINS
.
794
4.
AGELENA
OPULENTA
TOXINS
.
794
XXX
CONTENTS
II.
NONPEPTIDE
TOXINS
.
794
D.
CALCIUM
CHANNEL
TOXINS
FROM SNAKE
VENOMS:
TAICATOXIN
.
795
E.
TOXINS
WITH
CLAIMED
BUT
UNPROVEN
ACTION
ON
CALCIUM
CHANNELS
.
.
796
I.
MAITOTOXIN
.
796
II.
LEPTINOTOXIN-H
.
796
III.
GONIOPORA
TOXIN
.
796
IV.
APAMIN
.
797
V.
ATROTOXIN
.
797
F.
FUTURE
PROSPECTS
.
797
REFERENCES
.
799
CHAPTER
23
ADP-RIBOSYLATION
OF
SIGNAL-TRANSDUCING
GUANINE
NUCLEOTIDE
BINDING
PROTEINS
BY
CHOLERA
AND
PERTUSSIS
TOXIN
P.
G
IERSCHIK
AND
K.H.
J
AKOBS
.
WITH
2
FIGURES
.
807
A.
INTRODUCTION
.
807
B.
STRUCTURE-FUNCTION
RELATIONSHIPS
OF
CHOLERA
AND
PERTUSSIS
TOXINS
.
809
I.
CHOLERA
TOXIN
.
809
II.
PERTUSSIS
TOXIN
.
810
C.
STRUCTURE
AND
FUNCTION
OF
ADP-RIBOSYLATION
FACTORS
.
813
D.
MOLECULAR
MECHANISMS
OF
G-PROTEIN
ADP-RIBOSYLATION
BY
CHOLERA
AND
PERTUSSIS
TOXINS
.
816
I.
CHOLERA
TOXIN
.
816
1.
ADP-RIBOSYLATION
OF
GS
.
816
2.
ADP-RIBOSYLATION
OF
RETINAL
TRANSDUCIN
.
817
3.
ADP-RIBOSYLATION
OF
GJ/G
O
-LIKE
G
PROTEINS
.
818
II.
PERTUSSIS
TOXIN
.
820
1.
ADP-RIBOSYLATION
OF
RETINAL
TRANSDUCIN
.
820
2.
ADP-RIBOSYLATION
OF
GJ/G
O
-LIKE
G
PROTEINS
.
821
E.
FUNCTIONAL
CONSEQUENCES
OF
G-PROTEIN
ADP-RIBOSYLATION
BY
CHOLERA
AND PERTUSSIS
TOXINS
.
824
I.
ADP-RIBOSYLATION
OF
G
S
BY
CHOLERA
TOXIN
.
824
1.
SHORT-TERM
EFFECTS
.
824
2.
LONG-TERM
EFFECTS
.
825
II.
ADP-RIBOSYLATION
OF
G
PROTEINS
OTHER
THAN
G
S
BY
CHOLERA
TOXIN
.
826
III.
G-PROTEINS
ADP-RIBOSYLATION
BY
PERTUSSIS
TOXIN
.
828
F.
FUTURE
PERSPECTIVES
.
830
REFERENCES
.
830
CONTENTS
XXXI
CHAPTER
24
CLOSTRIDIUM
BOTULINUM
C2
TOXIN
AND
C.
BOTULINUM
C3
ADP-RIBOSYLTRANSFERASE
K.
A
KTORIES
.
WITH
1
FIGURE
.
841
A.
INTRODUCTION
.
841
B.
CLOSTRIDIUM
BOTULINUM
C2
TOXIN
.
841
I.
ORIGIN
AND
STRUCTURE
.
841
II.
THE
BINDING
COMPONENT
.
842
III.
THE
ENZYME
COMPONENT
.
842
IV.
FUNCTIONAL
CONSEQUENCES
OF
THE
ADP-RIBOSYLATION
OF
ACTIN
.
842
V.
CYTOPATHIC
EFFECTS
.
843
VI.
PHARMACOLOGICAL
ACTIONS
.
843
VII.
OTHER
ACTIN-ADP-RIBOSYLATING
TOXINS
.
845
C.
CLOSTRIDIUM
BOTULINUM
C3
ADP-RIBOSYLTRANSFERASE
.
846
I.
ORIGIN
AND
STRUCTURE
.
846
II.
ENZYME
ACTIVITY
.
846
III.
SUBSTRATES
.
847
IV.
ADP-RIBOSYLATION
OF
ASPARAGINE
.
848
V.
FUNCTIONAL
CONSEQUENCES
.
848
D.
CONCLUDING
REMARKS
.
849
REFERENCES
.
849
SUBJECT
INDEX
.
855 |
| any_adam_object | 1 |
| author_GND | (DE-588)11883696X |
| building | Verbundindex |
| bvnumber | BV009252651 |
| callnumber-first | R - Medicine |
| callnumber-label | RC347 |
| callnumber-raw | RC347.5 |
| callnumber-search | RC347.5 |
| callnumber-sort | RC 3347.5 |
| callnumber-subject | RC - Internal Medicine |
| classification_rvk | XI 2469 |
| ctrlnum | (OCoLC)30032851 (DE-599)BVBBV009252651 |
| dewey-full | 616.8/047 |
| dewey-hundreds | 600 - Technology (Applied sciences) |
| dewey-ones | 616 - Diseases |
| dewey-raw | 616.8/047 |
| dewey-search | 616.8/047 |
| dewey-sort | 3616.8 247 |
| dewey-tens | 610 - Medicine and health |
| discipline | Medizin |
| edition | 2. print. |
| format | Book |
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| id | DE-604.BV009252651 |
| illustrated | Illustrated |
| indexdate | 2024-08-14T01:24:55Z |
| institution | BVB |
| isbn | 3540578153 0387578153 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-006157844 |
| oclc_num | 30032851 |
| open_access_boolean | |
| owner | DE-29 DE-188 |
| owner_facet | DE-29 DE-188 |
| physical | XXXI, 874 S. Ill., graph. Darst. |
| publishDate | 1994 |
| publishDateSearch | 1994 |
| publishDateSort | 1994 |
| publisher | Springer |
| record_format | marc |
| series2 | Springer study edition |
| spelling | Selective neurotoxicity with 73 tables H. Herken ... (eds.) 2. print. Berlin u.a. Springer 1994 XXXI, 874 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Springer study edition 1. print. 1992 erschienen in: Handbook of experimental pharmacology ; 102 Neurotoxicology Neurotoxizität (DE-588)4123836-9 gnd rswk-swf Neurotoxizität (DE-588)4123836-9 s DE-604 Herken, Hans 1912-2003 Sonstige (DE-588)11883696X oth DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=006157844&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Selective neurotoxicity with 73 tables Neurotoxicology Neurotoxizität (DE-588)4123836-9 gnd |
| subject_GND | (DE-588)4123836-9 |
| title | Selective neurotoxicity with 73 tables |
| title_auth | Selective neurotoxicity with 73 tables |
| title_exact_search | Selective neurotoxicity with 73 tables |
| title_full | Selective neurotoxicity with 73 tables H. Herken ... (eds.) |
| title_fullStr | Selective neurotoxicity with 73 tables H. Herken ... (eds.) |
| title_full_unstemmed | Selective neurotoxicity with 73 tables H. Herken ... (eds.) |
| title_short | Selective neurotoxicity |
| title_sort | selective neurotoxicity with 73 tables |
| title_sub | with 73 tables |
| topic | Neurotoxicology Neurotoxizität (DE-588)4123836-9 gnd |
| topic_facet | Neurotoxicology Neurotoxizität |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=006157844&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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