Annual Review of Pharmacology and Toxicology 1993 - 1997: Vol 33-37 Index & Table of Contents

19 Pages·3.9 MB·English

SUBJECT INDEX
A antiobesity and antidiabetic Angiotensin-converting enzyme
drugs based on, 421, (ACE), 53-66, 131
ACE (See Angiotensin-converting 431-32, 438-40 deficient mice, 131
enzyme) cloning of gene and cDNA, inhibitors
Acetaminophen, 91-97 422-23 capropril, 56, 62-63
cytochromes P450 and, 92-96 comparison with 8), 62, 421-24 enalapril, 63, 65
hepatic necrosis induced by, number of residues kinnase-2 inhibitory
92-94 conserved, 424 properties of, 56
hepatotoxicity distribution, 430-33 lisinopril, 61-62
glutathione protective human mRNA and, 432-33 losartan, 61-63
against, 92 G, protein interaction site, ramipril, 65
mitochondrion and, 94-95 429-30 renal hemodynamics and, 55
protein adducts and, 93-97 ligand-binding saralasin, 55, 62
Actylation polymorphism, 269-77 site, 428-29 teprotide, 55
association with drug toxicity, studies, 421 Anoxia
271 ligands, 433-40 carbon monoxide
interethnic variability and structure, 433, 438 neuropathology and, 543
evolution, 276-77 pharmacology, 433-40 Antioxidants
molecular mechanism of, polymorphism in humans, biliverdin, 517, 522
271-76 428 Carolina rinse solution and, 327
NAT2 genetic variability, regulation of expression and estradiol, 483, 487-88, 496, 500
273-76 functions, 440-42 vitamin E, 488
NAT2 locus, 269-70, 272-7 thermogenesis, 421 Antisense RNA blockage, 124
Acetylcholinesterase, 84 f-Adrenergic receptor system, Apoptosis, 93, 243-44
N-Acetyltransferases, 269-70, 131-33, 421-47 mechanism of, 244
272-76 Adrenergic receptors, 421-47 Arachidonic acid, 182, 220
NAT2 polymorphism, 269-70, B, and B2, 421-22, 424, release
272-76 430-31, 439-41 mGluRs and, 220
Acidic fibroblast growth factor, (See also £3-Adrenergic L-Arginine, 340, 350-55
241 receptor) nitric oxide synthase and
Acupuncture, 23 Adult respiratory distress dimer assembly and,
Acute nervous system injury, syndrome (ARDS), 330 350-51
251-52 Affymax, 19-20 Arsenic
neurotrophic therapy for, 251 Ah receptor, 309 biotransformation of, 398-419
Acyl CoA cholesterol acyl Airway reactivity folic acid derivatives and,
transferase (ACAT), 482 cigarette sidestream smoke and, 413
Adenosine deaminase, 84 29-30, 45-47 genetic polymorphism and,
S-Adenosylmethionine (SAM), Alcoholic liver disease, 103-4, 403-5
398-400 methylated arsenic species,
Adenyl cyclase heme oxygenase-1 and, 529 400-19
Gp, subunit and, 185-86 Alzheimer’s disease dimethylarsonic acid
Addiction NGF therapy for, 250-51 (DMA), 400-2, 408,
as a brain disease, 26 6-Aminolevulvinate synthase 412-19
methadone treatment for, 14-20 (ALAS), 518, 535 diversity, 402-5
Addiction Research Foundation, Amodiaquine evolutionary significance,
16-18 hepatotoxicity and, 98, 106 402-5
Adipose tissue protein adduct, 106 monomethylarsonic acid
brown, 431-32, 438, 442-46 Amyotrophic lateral sclerosis (MMA), 400
white, 431-32, 438, 442-46 (ALS), 241, 244-47 methyltransferases, 397-98,
B3-Adrenergic receptor, 421-47 ciliary neurotrophic factor for 412-15
adenyl cyclase activation treatment of, 241, 245-46 genotoxicity, 414-15
studies, 421 insulin-like growth factor for intermediates, 412-13
adipose tissue and, 431-32, treatment of, 246 porphyrin profiles, 415
438, 442-46 Angiotensin protein binding and,
amino acide homology with in blood vessels or vascular bed, 413-14
other species, 424-28 58-61 uptake, 414
SUBJECT INDEX
toxicity, 397-416 Biliverdin reductase (BVR), 518, roles
cancer and, 398, 412 536 in cardiovascular system,
tolerance and, 411-12 Blood pressure regulation 541-42
Arsenite biotransformation, 403 renal renin-angiotensin system in immune system, 542-43
Arsine, 398, 410-11 blockage and, 57-58 in LTP and, 539-41
toxicity, 410-11 renin-angiotensin system and, in nervous system, 539-41
Asthma 53-58, 66 as signal molecule for
passive smoking and, 29-30, Brain-derived neurotrophic factor generation of cGMP,
45-47 (BDNF), 239, 242-43, 246, 530-33, 537-39
Atherosclerosis, 477-503 248-51 toxicity, 543-44
estrogen-mediated inhibition of, Bruton tyrosine kinase, 190 Carcinogenesis
477-85, 493-97, 501-2 pulmonary, 29-30, 33-35
cholesterol levels in plasma Cardiotrophin-1, 241
and tissue and, 480-85 C Cardiovascular disease
estrogen replacement and, estrogen and prevention of,
478-79, 501-2 Caffeine, 12-13 477-503
nitric oxide and, 493-97 Calcium ATPase pump, 186 estrogen replacement and,
fatty streak development, Calcium channel blockers 470-79
485-89, 495-96 benz(othi)azepines, 361, 364, Cardiovascular hypertrophy
foam cell formation, 485-89, 371-74 renin-angiotensin system
495-96 dihydropyridines, 361, 364, tissues and, 54
lipoprotein transport, 371-91 Carolina rinse solution
retention, and phenylalkylamines, 361, liver transplantation therapy
modification, 484-86 364-73 and, 327, 333-35
lipoprotein uptake, 485, [See also Benz(othi)azepines, Cell death, 93, 243-44
495-96 Dihydropyridines, cGMP (See Cyclic GMP)
monocyte adherence, Phenylalkylamines]} Cholinsterase, 5, 8
migration, and Calcium channels Chronic obstructive pulmonary
differentiation, 485, chimeric disease
495-96 identification of passive smoking and, 30, 35-36
gender differences in incidence dihydropyridine binding Cigarette sidestream smoke,
of, 477-79 regions using, 379-82 29-47
hypercholesterolemia and, Gay subunit and, 181-93 adverse effects on pre- and
480-85 L-type, 361-91 postnatal development, 29,
lesions, 480 diversity of cellular 36-47
advanced atherosclerotic, responses, 362 Clara cells and, 39-41
497-98 domain-interaction model for cytochrome P450 expression
formation of fibrofatty, allosteric modulation of, and, 38, 40
496-97 390 enzyme activity in bronchial
smooth-muscle contraction tree, 39-41
and, 361, 387-91 hepatic EROD activity, 39
B transmembrane segments intrauterine growth
IIIS6 and IVS6, 387-91 retardation, 29, 36-37
Behavior Calcium homeostasis NADPH reductase protein
drug-taking, 451-72 disruption of expression and, 38, 40
model for, 458 hepatotoxicity and, 93 carcinogenic potency, 33-35
(See also Compliance) Calmodulin (CaM), 340-53 cardiovascular changes, 36
Benz(othi)azepines, 361, 364, nitric oxide synthase and lung function changes, 41-47
371-74, 387-91 binding sites for, 340, 354 effector cell and, 43
binding site Cancer hyperresponsiveness to
access pathway to, 373 arsenic toxicity and, 398, 412 serotonin, 41
mutational analysis of, 374 chemotherapeutics rapidly adapting receptors
receptor site farnesyltransferase and, 45
biochemical localization of, inhibitors, 143-61 pulmonary effects, 35-36
373-74 Captopril, 56, 62-63 (See also Environmental
structure and selectivity, 371-72 Carbon monoxide tobacco smoke, Passive
voltage and state dependence of generation smoking)
Ca?*+ channel block, 371, heme oxygenase system and, Ciliary neurotrophic factor
373 517-45 (CNTF), 241-43, 251,
Bilirubin, 518 similarity to nitric oxide 253-55
Biliverdin, 518, 522 generating system, 529-30 amyotrophic neurotrophic
SUBJECT INDEX 557
factor therapy, 245-46 generation of, 530-33, localization of receptor site,
Clara cells 537-45 378-79
enzyme activity in bronchial heme oxygenase system and, molecular mechanism of
tree 517 high-affinity L-type Ca 2+
cigarette sidestream smoke Cyclic GMP-dependent activities channels and, 384-86
and, 39-41 carbon monoxide regulation of, voltage and state dependence of
Clinical trials 517, 530-33 action of, 374-75
compliance issues and, 451-52, Cyclic guanine monophosphate Dioxin receptors
468-72 (See Cyclic GMP) hsp90-based chaperone system
sample size and power Cyclosporin A, 298, 310-11 and, 297-98, 303, 309
intention to treat analysis, CYP2C genes, 287-88 Dioxin toxicity
469-71 CYP2D genes, 269-70, 279-84 transgenic mouse model, 136
new drug applications and, genetic variability, 279-84 Directly observed therapy (DOT),
471 functional alleles, 282-84 455
CLIX program, 78 null alleles, 280-82 Docking, 71-75
Cohn, Edwin J., 7 Cytochromes P450 structural databases
Colony-stimulating factor cigarette sidestream smoke and, lead compound generation
(CSF-1), 495 38, 40 and, 74-75
Compliance, 451-72 hepatotoxicity and Drinking water
clinical trials and, 451-52, acetaminophen-induced, arsenic in, 397-98
468-72 92-96 Drug abuse, 14—20, 26
intention to treat analysis, ethanol and, 103-4 heroin, 14-20
469-71 halothane and, 99 methodone treatment for,
compliance indices, 456 tienilic acid and, 102-3 14-20
cost of, 471 isozymes Drug acetylation
defined, 452-54 dibrisoquine-sparteine polymorphism (See Acetylation
method effectiveness, 453, polymorphism and, 269, polymorphism)
70-71 277-86 Drug design, structure-based (See
use effectiveness, 453, mephenytoin polymorphism Structure-based drug design)
470-71 and, 269, 286-88 Drug development
directly observed therapy, 455 compliance and, 451-52
drug development and, 451-72 electronic monitoring of,
exposure-response relationship, D 453-54
465-68, 472 Drug metabolism, 269-89
measuring, 453-55 Desmethyoxyverapamil, 364-71 Dynorphin, 8, 16-17, 21
monitoring Dibrisoquine-sparteine discovery of, 8
disclosure and, 460 polymorphism of drug peptides, 21
dosing frequency and, oxidation, 269-70, 277-86
462-63 interethnic variability and
duration, 462 evolution, 284-86 E
electronic, 453-72 molecular mechanism, 278-84
patient population variation, CPP2D genes, 269-70, Embryonic stem cell technology,
458-60 279-84 121, 126-30
pharmacokinetic parameters genetic variability, 279-84 Enalkiren, 63
and, 464 risk factor for certain diseases, Endothelial cells
Computational alchemy, 81-85 278 liver reperfusion injuries and,
Computational chemistry, 71-86 therapeutic consequences, 278 327-30, 335
Congestive heart failure Diclofenac Endothelium-dependent
renin-angiotensin system hepatotoxicity and, 105, 107 hyperpolarizing factor
tissues and, 54 protein adduct, 106 (EDHF), 500
Covalent binding, 91-109 Dihydralazine, 102-3 Endothelium-derived relaxing
hepatotoxicity and, 91-97 Dihydropyridines (DHPs), 361, factor (EDRF), 493
nephrotoxicity and, 98-99 364, 371-91 Environmental tobacco smoke
Cyclic AMP accumulation agonist and antagonist receptor as carcinogen, 29-30
mGluRs and, 218-19 sites, 386-87 carcinogenic potency, 33-35
Cyclic AMP responsive elements, identification of access effects on Clara cells, 39-41
423 pathway, 375-78 intrauterine growth retardation
Cyclic GMP individual amines acid residues and, 29, 36-37
accumulation and binding of mainstream smoke, 32, 41
mGluRs and, 219 site-directed mutagenesis measuring exposure of
carbon monoxide and studies of, 382-84 nonsmokers to, 32
58 SUBJECT INDEX
pulmonary effects, 35-36 nitric oxide synthases and, Glucocortical response element
sidestream smoke 339-55 (GRE), 524
(See also Cigarette sidestream Folic acid Glutamate receptors
smoke, Passive smoking) arsenic biotransformation and, ionotropic glutamate receptors
Epidermal growth factor (EGF) 413 (IGluRs), 205, 225
241, 253 Free-energy calculation metatropic glutamate receptors
Epinephrine perturbation method, 71, 83 (mGluRs), 205-27
early research, 4 thermodynamic integration G protein-coupled receptors,
Estradiol, 483, 487-88, 496, 500 method, 83 205-27
Estrogens, 477-503 Free-radical immunoassay, 20 G protein-linked receptors,
altered vasomotion and, Free radicals, 244, 517 167-93
498-502 nitric oxide, 392, 493-97, GDP, 169
therapeutic implications of, 517-30 GTP, 16°
501-2 olfactory
antioxidant effects of, 4 G visual syste:
486-89 rhodopsin,
atherosclerosis and, 4 77-503 Gaddum, John, 7-8 G proteins, 167
cholesterol levels in plasm: GDP, 169 By subunits
and tissues, 480-85 Geldanamycin, 308, 315-16 hsp90 chaperoning :
formation of fibrofatty Gene targeting, 121-37 316-18
lesion, 496-97 design of vectors, 126-29 G protein signal transducti
gender differences in embryonic stem cell system, 167-93
incidence of, 477-79 technology, 121, 126-30 effectors, 167, 178-90
equine, 501-2 (See also Transgenic technology) specificity of, 180
estrogen replacement therapy, Genetic polymorphisms, 269-89 G, subunits, 167, 169,
477-79, 501-2 acetylation, 269-77 176-78
progestins and, 497, 501 clinical relevance, 271 Gay subunits, 167-93
Ethanol interethnic variability and B and y assembly, 173-74
alcoholic liver disease and, evolution, 276-77 B and y interactions, 173
1034, 106 molecular mechanism, effector targets, 178-90
liver grafts and use of, 327, 333 271-76 lipid modification, 174-75
335 NAT1, NAT2, 269-70, localization, 176
Ethoxyresorufin-O-dealylase, 272-76 phosphorylation, 175-76
38-39 defined, 270 proteins interacting with,
Euro-Collins solution, 329 dibrisoquine-sparteine, 269-70, 191-93
Excitotoxicity 277-86 structure, 169-73
mGluRs and reducing, 292 5 clinical relevance, 278 in vesicular traffic, 187-88
Exposure-response relationships cytochrome P450 CYP2D WD-repeat, 170
noncompliance and, 465-68, genes, 269-70, 279-84 GRID program, 78
472 interethnic variability and GROW method, 76-77
evolution, 284-86 Growth factors
F molecular mechanism, epidermal (EGF), 241, 253
278-84 fibroblast(bFGF), 241, 251-52
mephenytoin, 269-70, 286-88 acidic (aFGF), 241
Farnesylation clinical relevance, 286-87 insulin-like (IGF), 241, 246,
G,, subunit and, 174-75 interethnic variability and 248, 252-53
Farnesyl-protein transferase evolution, 288 nerve (NGF), 239, 243, 247-48,
(FPTase), 143-61 molecular mechanism, 253-57
Farnesyltransferase inhibitors 287-88 non-neurotrophin, 242
143-61 Geranylgeranylation, 143, 147, transforming (TGF), 240-41
efficacy against ras-transformed 158-59, 174-75 GTP, 169
cells, 153-54 G, subunit, 174-75 Guanine nucleotide diphosphate
selectivity for tumor cells, Geranygerany]-protein transferase (GDP), 169
157-58 types I and II, 148 Guanine nucleotide binding
structural diversity, 149-51 Glial cell-derived neurotrophic proteins (See G proteins)
Ferrochelatase, 518 factor (GDNF), 241, 243, Guanine nucleotide triphosphate
Fibroblast growth factor (bFGF) 248-56 (GTP), 169
241, 251-52 Parkinson’s disease and, 248-50 Guanosine monophosphate, cyclic
acidic (aFGF), 241 Glycine, 327, 333-35 (See cGMP)
FK506, 298, 310-11 Carolina rinse solution and, Guanylate cyclase, soluble (See
Flavoproteins 327, 333-35 Soluble guanylate cyclase)
SUBJECT INDEX
H in liver, 528-29 FK506-binding proteins,
in reproductive system, 528 310-11
Halothane, 91, 99-102 Hemeprotein functions, 312
hepatitis and, 99-102 nitric oxide synthases and, Inhalation anesthesia, 10-11
hepatotoxicity and, 99-102 339-55 Insulin-like growth factor (IGF),
protein adducts, 99-102 promotion of dimer assembly 241, 246, 248
Heat-shock nuclear factor, 524 of, 352 acute nervous system injury
Heat-shock protein (HSP), Heparin-binding neurotrophic and, 251
297-318, 518 factor ( = pleotrophin), 241 amyotrophic lateral sclerosis
(See also Heme oxygenase-1) Hepatic necrosis therapy, 246
Heat-shock protein (hsp) 90-based acetaminophen-induced, 92-94 Intention to treat (ITT) analysis
chaperone system, 297-318 Hepatic parenchymal cells, 329 compliance and, 469-71
dioxin receptors and, 297-98, Hepatitis Intercellular adhesion molecule |
303, 309 dihydralazine and, 102-3 (ICAM-1), 490
G protein By subunit and, halothane and, 99-102 Intermediate density lipoproteins
316-18 Hepatotoxicity (IDLs), 481-85
hsp heterocomplex assembly acetaminophen-induced, 91-97 International Narcotic Research
system, 298-302 amodiaquine and, 98 Conference, !5
components, 299-300 butylated hydroxytoluene and, Inward rectifier G protein—gated
mechanism, 300-2 97 K* channel, 181-83
immunophilins, 297-98, diclofenac and, 105-7 lonotropic glutamate receptors
309-12 ethanol and, 103-4, 106 (iGluRs), 205
cyclosporin A-binding glutathione protective against, Iron-responsive elements, 535
protein, 311 92 Ischemic stroke
FK506-binding proteins, halothane and, 91, 99-102 neurotrophic therapy for,
310-11 methapyrilene and, 97 251-52
functions, 312 possible mechanisms of, 93
immunophilin binding site, Heregulins, 241 K
311-12 Heroin addiction, 14-20
MAP kinase system and, 298, methadone treatment for, 14-20
Kidney
307, 313-15 HIV protease
renin-angiotensin system of,
steroid receptors and, 297-98, crystallographic structures of,
53-66
303-18 83-84
renal hemodynamics and, 55
hormone-binding domain, nonpeptide-based inhibitors
Krayer, Otto, 8-9
303-4 design of, 72-74, 78
Kuppfer cells, 93, 327-35
receptor trafficking, 307-9 HOOK program, 76
activation of
required for normal signal Hormone replacement therapy,
hepatotoxicity and, 93
transduction, 305-7 478-79, 501-2
liver reperfusion injuries and,
steroid binding site, 304-5 Hsp90 (See Heat-shock protein
327-30
Hematin, 520 90-based chaperone system)
inflammatory mediators
Heme Human umbilical vein endothelial released by, 329-30
free, 519 cell (HUVEC), 490, 497
“cytokine storm,” 329-30
ligand interactions, 519-45 Hyaluronic acid, 85-86
Heme oxygenase (HO) system, 3-Hydroxy-3 methylglutary]
517-45 coenzyme A reductase L
isozymes of (HMG CoA reductase), 482
carbon monoxide produced Hypercholesterolemia, 480 L-Cysteine-sulfinic acid (L-CSA),
by, 517-45 Hypertension, 54 220
molecular properties of, renin-angiotensin system Lead compound discovery
522-24 tissues and, 54 3-D database methods, 78-79
reciprocity with nitric Hypertension docking from structural
oxide—generating system, mGluRs and regulation of, 227 databases and, 74-75
533-36 generation from fragment
regulation, distribution, and methods, 75-78
development, 524-29 I GROW method, 76-77
Heme oxygenase-1 (Heat-shock HOOK program, 76
protein) and -2, 517-45 Immunophilins, 297-98, 309-12 LUDI algorithm, 76
distribution hsp90-based chaperone system MCSS program, 75-76
in brain, 525-27 binding site, 311-12 Monte Carlo De Novo
in cardiovascular system, cyclosporin a—binding Ligand Generator, 77
528 protein, 311 SPROUT program, 77-78
560 SUBJECT INDEX
molecular visualization and Lung cancer adenylcyclase inhibition, 218
modeling of, 72-74 passive smoking and, 29-30, cAMP accumulation, 218-19
simplified potential energy 33-35 cGMP accumulation, 219
functions and, 79-81 Lysine, arginine, ornithine binding phosphoinositide hydrolysis,
Lead compound refining and protein, 216 218
reengineering, 81-86 regulation of synaptic
alchemical free-energy changes, M transmission, 222-25
82-85 Metallothionein, 123
determination of positions of Macrophage colony-stimulating Methadone, 14-20
tightly bound waters, factor (MCSF), 492 long-acting, 17-18
85-86 MAP (mitogen-activated protein) Methapyrilene, 97, 106
perturbation method of kinase, 217 Methoxyverapamil, 364-71
free-energy calculation, , MAP kinase cascade, 153 1-Methyl-4-phenylpyridinium
83 Gay subunit and, 188-89 (See MPPt)
thermodynamic integration MAP kinase system, 298, 307, Methyltransferase
method, 83 313-15 arsenite, 397-98, 412-15
Lecithin cholesterol acyl Medullipin, 57 genotoxicity, 414-15
transferase (LCAT), 481-82 Memory impairment intermediates, 412-13
Leptin mGluR ligands and, 226 porphyrin profiles, 415
metabolism and, 444, 446 Menopause, 478, 501-2 protein binding, 413-14
Leucine, isoleucine, valine binding Mephenytoin polymorphism, uptake, 414
protein (LIVBP), 215-17 269-70, 286-88 mGluRs (See Metabotropic
Leukemia inhibition factor (LIF), clinical relevance, 286-87 glutamate receptors)
126 interethnic variability and Military medicine, 5-6
Leukocyte inhibitory evolution, 288 Mitochondrion
factor/cholinergic molecular mechanism, 287-88 as organelle of
differentiation factor, 241 CYP2C genes, 269-70, acetaminophen-induced
Lipid metabolism 287-88 hepatotoxicity, 94-95
B3-adrenoreceptor and, 421, CYP2C19 alleles, 287-88 Mitogen-activated protein (See
431-47 Metabotropic glutamate receptors MAP)
Lisinopril, 61, 62 (mGluRs), 205-27 Molecular biology
iver transplantation therapy clinical potential, 225-27 early, 11-12
Carolina rinse solution and, antiepileptic, 226 Molybdate, 307-8
327, 333-35 cognitive enhancement and, Monocyte chemoattractant protein
endothelial cell killing and, 226 (MCP-1), 492-94
328-30, 335 hypertension and, 227 Monte Carlo De Novo Ligand
graft failure and, 332-33 movement disorders and, 226 Generator, 77
Kupffer cell activation and, pain and, 227 Movement disorders
328-35 reducing excitotoxicity with, mGluR ligands and treatment
pH paradox and, 330-31 225 of, 226 MPP*, 248
reperfusion injury and, 327-3: cloned, 206-27 MPTP, 249
Apoprotein(a), 483 glutamate binding site, Multiple sclerosis
Apoproteins 215-16 neurotrophic therapy for,
high-density (HDL), 477, G-protein coupling, 216-17 252-53
481-85, 489 human homologues, 208 insulin-like growth factor 1,
intermediate density (IDL) intramolecular transduction, 252-53
481-85 217 Muscarinic (acetylcholine)-gated
low-density (LDL), 477, pharmacology, 210-14 K* channel
481-95 splice variants, 206-8 Gry subunit and, 181-83
estrogen and prevention of structure, 214-15
oxidation of, 477 transduction mechanisms, N
oxidation of, 488-89 208-10
role of nitric oxide in regulation of ion channels and NADPH
oxidation of, 495 cell excitability, 220-22 nitric oxide synthases and
very low density(VLDL), 477, potassium channel binding sites for, 340-55
481-85, 489 modulation, 220-21 NADPH-cytochrome P450
Long-term potentiation voltage-dependent calcium reductase, 341, 522
carbon monoxide’s role in, channel modulation, NADPH reductase protein
539-41 221-22 expression
Losartan, 61-63 regulation of second cigarette sidestream smoke and,
LUDI algorithm, 76 messengers, 218-20 38, 40
SUBJECT INDEX 561
NAT2 gene estrogen-mediated inhibition of polymorphism of human, 44
genetic variability, 273-76 atherosclerosis and, heredity and, 444, 446
decreased function alleles, 493-96 leptin receptor and, 446
273-75 monocyte adherence and OncoMouse models of dioxin
functional characterization of migration and, 493-95 toxicity, 136
mutant alleles, 275-76 role in oxidation of Opioids
locus, 269-70, 272-76 low-density lipoprotein, dynorphin, 8, 16-17
Nephrotoxicity, 98-99 495 endogenous opioid peptide
Nerve growth factor (NGF), 239, Nitric oxide synthase (NOS), acupuncture and, 23
243, 247-48, 253-57 339-55, 494-96, 518, 520, receptors, 14-16
nervous system injury 534, 540 Oxidation
treatment, 251-52 bi-domain organization, low-density lipoprotein
sensory neuropathy treatment prosthetic group, and estrogen and prevention cf,
and, 247-48 substrate binding sites, 477, 486-89
Neuregulins, 241 340-43 Oxidative stress, 93-98, 244,
Neurotrophic factors, 239-57 dimeric, 346-55 517-32, 544
brain-derived (BDNF), 239, dimer assembly and heme oxygenase and, 517-32,
242-43, 246, 248-51 L-arginine analogs, 544
ciliary (CNTF), 241-43, 251, 350-51 heme production and, 532
253-55 dimeric interaction and nephrotoxicity and, 98
glial cell-derived (GDNF), 241, heterodimer formation, hepatotoxicity and, 93
243, 248-56 351-52 sudden infant death syndrome
heparin-binding, 241 dissociation and unfolding (SIDS) and, 544
long-term potentiation and, 243 of, 346-48
neuroprotection mechanisms, heme-containing monomers P
243-44 and, 350
pharmacology, 253-57 heme-free NOS monomers Parkinson’s disease, 241, 248-50,
intracerebral administration, and, 348-50 254
254-55 endothelial (eNOS), 494 GDNF and 241, 248-50
small molecule mimetics, expression in cytokine-activated neurotrophin therapy for,
255-57 cells, 352-54 248-50
physiologic function, 242-43 heme oxygenase system and, Passive smoking
therapeutics, 244-53 518, 520, 534, 540 asthma and, 30
acute nervous system injury, reductase and oxygenase cardiovascular disease and, 30,
251-52 domains, 343-46 36
Alzheimer’s disease, 250-51 catalysis of mixed-domain children and
amyotrophic lateral sclerosis, system, 345-46 lung function in, 41-47
244-47 catalytic properties of respiratory effects in, 29-47
ischemic stroke, 251-52 isolated domains, 344—45 chronic obstructive pulmonary
multiple sclerosis, 252-53 oxygenase domain active disease and, 30, 35-36
Parkinson’s disease, 248-50 site, 344 (See also Cigarette sidestream
sensory neuropathy, 247-48 S-Nitroso-N-acety] penicillamin, smoke, Environmental
Neurotrophin-3 (NT3), 239, 242, 497 tobacco smoke)
246, 248, 251, 254 Non-insulin-dependent diabetes Perindopril, 64
Neurotrophin-4/5 (NT4/5), 239, (NIDDM) Periodate-oxidized adenosine, 398
246-49, 251 §3-adrenergic receptor and, 421, Periplasmic binding proteins
New drug applications, 471 431-32, 438-40, 442-46 (PBP), 215-17
Nicotine, 32-33 polymorphism of human, PH domains, 191-93
Nicotine-derived nitrosamine 444 Phenolphthalein analogs, 75
ketone (NNK), 40 Non-neurotrophin growth factors, Phenylalkylamines, 361, 364-71,
Nitric oxide (NO), 392, 493-97, 242 387-91
517-30 Noradrenaline receptor, 423 high-affinity binding, 369-71
activity Norepinephrine mutations in tranmembrane
reciprocity with heme early research, 7 segment IVS6, 369-70
oxygenase system, 533-36 receptor site
regulation of, 517-21 O access pathway to, 366-67
similarities to carbon biochemical localization of,
monoxide generating Obesity 367
system, 529-30 §3-adrenergic receptor and mutational analysis of,
soluble guanylate cyclase regulation of, 421, 431-32, 367-69
activation by, 520 438-40, 442-46 structure and selectivity, 364
562 SUBJECT INDEX
verapamil, 364-71 protein prenylation reactions, SPROUT program, 77-78
voltage and state dependence of 146 Steroid receptors
Ca?+ channel block, ras-induced cell transformation heat-shock protein 90
364-66 farnesyl-protein transferase and, chaperones and, 297-98,
Phosducin, 191 144-61 303-18
Phosphoinositide hydrolysis, 209, ras oncogenes hormone binding domain,
218 farnesyltransferase inhibitors 3034
Phosphoinositide-3 kinase and, 143-61 receptor trafficking, 307-9
Gp, subunit and, 189-90 Receptor kinases required for normal signal
Phospholipase Gay subunit and, 186-87 transduction, 305-7
A, 220 Renin-angiotensin system (RAS) steroid binding site, 304-5
A2 tissues, 53-66 immunophilin chaperones and,
Gay subunit and, 183 access to site of angiotenin II 298, 309-12
production, 64-65 Structure-based drug design,
hydrolysis, 209 blockade by ACE inhibitors, 71-86
CB 53-57 lead compound discovery,
Gay subunit and, 183-85 cardiovascular hypertrophy and, 71-81
D, 220 54 3-D database methods,
novel metabotropic receptor contractility and, 61-62 78-79
coupled to, 220 growth and, 62-63 docking from structural
Pleotrophin (= heparin-binding hypertension and, 54 databases and, 74-75
neurotrophic factor), 241 in kidney, 53-66 generation from fragment
Porphyrin, 519-30 sodium reabsorption, 53 methods, 75-78
ring, 519 partitioning of renal, 59-60 molecular visualization and
Potassium channels, 181-83, renin inhibitors, 63-65 modeling of, 72-74
220-21 Reperfusion injury simplified potential energy
mGluRs and modulation of, liver transplantation and, functions and, 79-81
220-21 327-35 lead compound refining and
muscarinic reengineering, 81-86
(acetylcholine)-gated, S alchemical free-energy
181-83 changes, 82-85
Progestins S-adenosylmathionine, 398 determination of positions of
with estrogen replacement Saralasin, 55, 62 tightly bound waters,
therapy, 497, 501-2 Sex-hormone-binding globulin, 85-36
Protein adducts, 91 486 perturbation method of
xenobiotic Signal transduction, 167-93 free-energy calculation,
acetaminophen, 93-97 G protein (See G protein signal 71, 83
butylated hydroxytoluene, 97 transduction system) thermodynamic integration
halothane, 99-102 heat-shock protein 90 and, method, 83
in kidney, 98-99 297-318 Sulisobenzone, 75
methapyrilene, 97 (See also Heat-shock protein Superoxide dismutase, 245, 494
tienilic acid, 102-3, 106 90-based chaperone Synaptic transmission
Protein chaperone (See system) mGluRs and, 205, 222-25
Heat-shock protein 90—based Smoking presynaptic autoreceptors at
chaperone system) passive (See Passive smoking; glutamatergic synapes,
Protein folding see also Cigarette
heat-shock protein 90-based sidestream smoke, Systemic inflammatory response
chaperone system and, Environmental tobacco syndrome, 329-30
297-98 smoke) Syva, 19-20
Protein prenylation, 145-61 Smooth muscle contraction
enzymes that catalyze, 148 L-type Ca*+ channels and, T
p75-NGFR, 239-40 361-91
S-nitroso-N-acetyl penicillamin Tamoxifen, 501
R (SNAP», 497 Teprotide, 55
Sodium nitropruside, 497 Tetradecapeptide, 62
Raloxifene response element, Sodium reabsorption, 53 Tetrahydrobioterin (H4 biopterin)
491 Soluble guanylate cyclase (sGC), nitric oxide synthases and,
Ramipril, 65 518-21, 537 339-55
Ras activation by nitric oxide, 520 promotion of dimer
exchange factor regulation by heme oxygenase assembly, 352
Gg, subunit and, 190 system, 530 Thermogenesis
SUBJECT INDEX 563
B3-adrenergic B-adrenergic receptor V
receptor-induced, 421, system, 131-33
431-40 embryonic stem cells, 121,
Valsartan, 57
Thymidylate synthase, 84 126-30
Vascular cell adhesion molecule-1
inhibitors, 74-75 hormone receptors, 134-35
(VCAM-1), 489-94
Tienilic acid, 102-3, 106 lipoprotein metabolism,
Vasodilation
Transforming growth factor-a, 131-33
240-41 peptide hormones, 134-35 estrogens and promotion of,
477
Transgenic mice (See Transgenic receptor activation, 133-34
Voltage-gated ion channels,
technology, transgenic renin/angiotensin system
181-83, 361-91
animal models; see also Gene and, 131-32
(See also Calcium channels,
targeting, OncoMouse model tumor immunotherapy,
Potassium channels)
of dioxin toxicity) 135-36
Verapamil, 364-71
Transgenic technology (See also Gene targeting)
Vinculin, 176
embryonic stem cell isolation, Transplantation
121, 125-30 liver reperfusion injury after
gene targeting, 121-30 liver preservation, 327-35 Ww
pharmacologic applications, Trichloroethylene, 91, 104-6
130-37 protein adducts, 106 WD-repeat, 170, 174
cancer, 135-36 Trk—type protein kinase receptor,
cardiovascular, 131-33 239, 242, 246
endocrine system, 134-35 Trypanothione, 405-6
nervous system, 133-34 Tumorigenesis, 143
toxicology, 136 Tumor necrosis factor, 490, 495, Xenobiotics, 91-109
pronuclear DNA injection, 497
122-30 Tumor necrosis factor-a, 329, 332,
antisense RNA blockage, 334 Z
124-25
gene regulation, 125 Zaffaroni, Alex, 19-20
inducible promotor systems, U Zankiren, 63
123 Zidovudine
transgenic animal models, University of Wisconsin solution, patient compliance and,
120-21, 125-37 327-28 456-57, 460