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Content, author and subject index
PHARMACOLOGY & THERAPEUTICS Volume 44
Executive Editors
W. C. Bowman, A. M. Breckenridge and A. C. Sartorelli
PERGAMON
PRESS
OXFORD . NEW YORK . BEIJING . FRANKFURT sAo PAUL0 . SYDNEY . TOKYO . TORONTO
PHARMACOLOGY &THERAPEUTICS Chemotherapy,
Toxicology
and Metabolic Inhibitors
Executive Editor: A. C. Sartorelli Yale University School of Medicine, Department of Pharmacology, New Haven, Connecticut 06510, USA
333 Cedar Street,
Associate Editor: Barbara Z. Renkin, Ph.D. General and Systemic Pharmacology
Executive Editor: W. C. Bowman University of Strathclyde, Department of Physiology & Pharmacology, 204 George Street, Glasgow Gl lXW, Scotland
Clinical Pharmacology
Royal College,
and Therapeutics
Executive Editor: A. M. Breckenridge University of Liverpool, Department of Pharmacology Liverpool L69 3BX, England
& Therapeutics,
P.O. Box 147,
Library Annual Subscription Rates-published in 4 volumes per annum of 3 issues each. Annual Subscription, 1990, DM 2370.00 including postage and insurance, 2 years, 1990/91, DM 4503.00. Specially Reduced Rates fo Individuals: Any individual whose institution takes out a library subscription may purchase a second or additional subscription for personal use at a much reduced rate of DM 740.00 annually. Subscribers to the Journal may claim a 20% discount off Encyclopedia volumes. Prices are subject to change without notice. Subscription enquiries from customers in North America should be sent to Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523, USA, and for the remainder of the world to Pergamon Press plc, Headington Hill Hall, Oxford OX3 OBW, England. At the end of the year, the Subscriber
will receive, free, the annual
subject
index.
It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. By submitting a manuscript, the authors agree that the copyright for their article is transferred to the publisher if and when the article is accepted for publication. However, assignment of copyright is not required from authors who work for organisations which do not Permit such assignment. The copyright covers the exclusive rights to reproduce and distribute the article, including reprints, photographic reproduction, microform or any other reproduction of similar nature and translations. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, electrostatic, magnetic tape, mechanical photocopying recording or otherwise, without permission in writing from the copyright holder.
Photocopying Information for Users in the USA. The Item-Fee Code for this publication indicates that authorization to photocopy items for internal or personal use is granted by the copyright holder for libraries and other users registered with the Copyright Clearance Center (CCC) Transactional Reporting Service provided the stated fee for copying, beyond that permitted by Section 107 or I08 of the United States Copyright Law, is paid. The appropriate remittance of $0.50 per page is paid directly to the Copyright Clearance Center Inc., 27 Congress Street, Salem, MA 01970. Permission for other Use. The copyright promotion, for creating for such copying.
owner’s consent does not extend to copying for general distribution, for new works, or for resale. Specific written permission must be obtained from the publisher
Publishing and Advertising Offices Pergamon Press plc Headington Hill Hall Oxford OX3 OBW England
Pergamon Press Inc. Maxwell House Fait-view Park, Elmsford New York 10523, USA
Volume 44,1989,
Numbers l-3
CONTENTS
PAGE
Number 1 Eicosanoids and airway smooth muscle: P. J. Gardiner Photoaffinity labeling of melanocyte-stimulating hormone receptors: A. N. Eberle, P. N. E. de Graan, T. Scimonelli and F. Solca Asparagine-linked oligosaccharides and tumor metastasis: A4. J. Humphries and K. Olden Inhibitors of DNA gyrase: K. Drlica and S. Coughlin Models and markers used to study cardiac reperfusion injury: J. P. Kehrer and J. W. Starnes
1 63 85 107 123
Number 2 Genetic factors influencing the metabolism of tolbutamide: D. J. Back and M. L’E. Orme Peripheral dopaminergic nerves: C. Bell The uses and limitations of calmodulin antagonists: M. L. Veigl, R. E. Klevit and W. D. Sedwick The pharmacology of (pi- and a,-adrenoceptors: Evidence for and against a further subdivision: J. R. Docherty Superoxide dismutase: Its role in xenobiotic detoxification: A. T. Canada and E. J. Calabrese Catalase: Its role in xenobiotic detoxification: E. J. Calabrese and A. T. Canada
147 157 181 241 285 297
Number 3 Clinical pharmacology of anxiolytics and antidepressants: A psychopharmacological perspective: D. J. Nutt and P. Glue Biological and chemical properties of the hemoregulatory peptide and possibilities for clinical applications: 0. D. Laerum and W. R. Paukovits Immunological aspects of diabetes mellitus: Prospects for pharmacological modification: M. Itoh Intestinal drug absorption enhancement: An overview: E. J. van Hoogdalem, A. G. de Boer and D. D. Breimer Nifedipine: Variability in its kinetics and metabolism in man: D. D. Breimer, J. H. M. Schellens and P. A. Soons
111
309 335 351 407 445
AUTHOR INDEX Back, D. J. 147 Bell, C. 157 Breimer, D. D. 407,445
Kehrer, J. P. Klevit. R. E. Laerum,
Calabrese, E. J. 285,297 Canada, A. T. 285,297 Coughlin, S. 107
Gardiner, Glue. P. Humphries, Itoh, M.
Paukovits,
M. J.
335
309
Olden, K. 85 Orme, M. L’E. W. R.
147 335
Schellens, J. H. M. 445 Scimonelli, T. 63 Sedwick, W. D. 181 Solca, F. 63 Soons, P. A. 445 Starnes, J. W. 123
63
P. J. 309
0. D.
Nutt, D. J.
de Boer, A. G. 407 de Graan, P. N. E. 63 Docherty, J. R. 241 Drlica, K. 107 Eberle. A. N.
123 181
1
85 van Hoogdalem, E. J. Veigl, M. L. 181
351
iv
407
SUBJECT INDEX Absorption enhancement, intestinal drugs 407-33 Adenylate cyclase, a,-adrenoceptors 266-68 Ageing a-adrenoceptor responsiveness 268 catalase 303, 304 superoxide dismutase activity 290-92 Airway smooth muscle eicosanoid action 4651 AMP 49, 50 calcium 47-49 inositol phospholipid 50 and eicosanoids l-52 biosynthesis 2-4 biosynthetic scheme 3 hyperactivity and eicosanoids 32-35 isolated and eicosanoids 7-36 cat 18, 19 dog 19-21 guinea pig 8-12 human 22-31 monkey 21,22 rat 16, 17 metabolism 4-7 uptake 4 Antidepressants anxiety 318-22 clinical pharmacology 309-27 mechanism and noradrenergic function 324, 325 Anxiety benzodiazepines 317 and depresssion relationship 312-14 diagnostic classification 309-11 tricyclic antidepressants 322, 323 Anxiolytics, clinical pharmacology 309-27 Asparagine-linked oligosaccharides, tumor metastases 85-99 Asthmatics, leukotiienes and airways in man 30, 31 Autoantibodies, serum in diabetes 355-61 Autoimmunity 352, 353 Azone, gastrointestinal absorption enhancement 429,430
drug target 187 nuclear magnetic resonance 207-10 -regulated enzymes 183-87 spectroscopic studies 204-207 structure 181, 182 structure-function probes 203-l 1 Calmodulin antagonists 181-229 anticancer agents 218, 219 binding properties 196-99 calmodulin activity 212-14 DNA interactive drug modification 219-25 bleomycin 221, 223, 224 DNA repair 222-24 hydrophobic 200-202 inhibitory properties 196-99 neuroleptic drugs 217, 218 peptides 203 pharmacodynamics 214-17 pleiotropic drug resistance 225-28 structure 188-95 therapeutic uses 214-19 types 187 Cardiac reperfusion injury age 132-34 cell culture 126, 127 definition 123, 124 hypoxia 130, 131 in vitro 126-30 markers 125 experimental 135-38 mechanisms 138 models 124, 126 pathways 139, 140 perfused preparation 128-30 Purkinje fiber 127, 128 Carnitine derivatives and gastrointestinal absorption 430 Castanospermine structure 96 Catalase age effects 303, 304 disease 299 genetics 298 inducers 299, 300 inhibition 300, 301 peroxisome 301 species variability 302, 303 toxicology 298 xenobiotic detoxification 297-304 Clomipramine, panic patients 320 Coumarins DNA replication 108 DNA supercooling 108 eukaryotic effects 109, 110 Cyclosporin, diabetes prevention 377-79 Cytoskeleton and calmodulin 183
Benzodiazepines, anxiety 317, 318 Bile salts, gastrointestinal absorption enhancement 418-20 Calcium a-adrenoceptors 265, 266 hypoxia and ischaemia markers 137, 138 Calcium binding agents, gastrointestinal absorption enhancement 427, 428 Calmodulin activities and antagonists 212-14 antagonist specificity 210, 211 circular dichroism 207 drug binding sites 201
Depression anxiety coexistence 313, 314 diagnostic classification 311-13 pharmacology 316 V
vi
SUBJECT INDEX
Diabetes, a-adrenoceptor responsiveness 269 Diabetes mellitus autoantibodies 355-61 anti-insulin 358 islet cell cytoplasmic 355-57 islet cell surface 357, 358 HLA-D region 353-55 immune complexes 361, 362 immunological aspects 351-82 DNA damage alkylating agent toxicity 224, 225 calmodulin inhibitors 221-25 DNA gyrase inhibitors 107-16 bacterial cell sensitivity factors 114 cell death 114 lesion repair 113 mutations and survival 115, 116 Dopaminergic neurons, peripheral 157-75 biochemical features 158-60 distribution 16675 gastrointestinal 172, 173 kidney 166-71 lung 173, 174 reproductive 173 histochemical features 160-63 identification 157-66 pathway 158 pharmacological features 164-66 ultrastructural features 163, 164 Drug interactions, tolbutamine metabolism I50-53 Eicosanoids, airway smooth muscle l-52 Enamines, gastrointestinal absorption 424, 425 Fatty acids, gastrointestinal
absorption
421, 422
Gastrointestinal drug absorption 407409 barriers 409-I 1 enhancers 41 l-32 structure 407409 Glycerides, gastrointestinal absorption 422-24 Glycoprotein processing, metastatic cells 86-88
Hemoregulators, peptide 335-46 chemical properties 336 clinical applications 345, 346 history 335, 336 monomer-dimer regulatory system properties 339-%2 purification 337
342-44
Imipramine, panic attacks 319 Immune complexes in diabetes 361, 362 Inhibitors DNA gyrase 107-16 metastatic 94-99 Insulin-dependent diabetes mellitus (IDDM) animal models 369-77 NOD mouse 375, 376 NZB mouse 376, 377 spontaneous 372-75 streptozotocin 369-71 free radical scavengers 38&82 immunosuppression 379, 380
lymphocyte reconstitution 379 prevention 377-82 Insulitis antiimmune responses 363 killer cells 367, 368 lymphocyte function 368 macrophages 366 T lymphocytes 36466 Kidney, dopaminergic neurons function 167-70 pathophysiology 171, 172
166-72
Lectin-resistant mutants, metastatic potential 91-94 Leukotrienes airways smooth muscle hyperactivity 35, 36 guinea pig airways smooth muscle 12-15 human isolated smooth muscle 27-30 metabolism 6, 7 rat isolated smooth muscle 17 therapeutic uses 52 Liposomes, gastrointestinal absorption 428, 429 Malignancy markers 90 Melanocyte stimulating hormone (MSH) features 63, 65 photoaffinity labels 65 biological activity 67 derivatives 66 structures 64 Melanophores, U.V. irradiation 68, 69 apparatus 69 Metastases see also tumor metastases functional defects 93, 94 glycoprotein processing inhibitors 94-99 lectin-resistant mutants 91-94 Mixed micelles, gastrointestinal absorption 425-427 Models cardiac reperfusion injury 124, 126 diabetes 369-77 Monoamine oxidase inhibitors, panic attacks 320, 321 Multipotent stem cells 340 Myelopoietic progenitor cells 339, 340
Nifedipine area under curve 448, 449 biotransformation 446 excretion 447 pharmacokinetics 449 population studies 445-50 variability in disposition kinetics 450-52 Non-steroidal anti-inflammatory drugs, gastrointestinal absorption 413-16 Nuclear magnetic resonance, calmodulin 207-10
Panic attacks 316, 319, 320 combination pharmacotherapy 321 psychological treatment 325, 326 Phenothiazines, gastrointestinal absorption 428 Photoafflnity labeling, MSH receptors 63-80 melanoma cells 76-79 melanophores 67-76
SUBJECI- INDEX Polyacrylic acid, gastrointestinal absorption enhancement 431. 432 Prostanoids see alsomuscle eicosanoids airways smooth 1. 2 therapeutic uses 51, 52 Protein kinases and calmodulin
184
Quinolones bacterial DNA 110,111 1I1 DNA supercooling DNA synthesis inhibition
112
Receptors. alpha, adrenergic agonist. therapeutic uses 270, 271 antagonist uses 271-73 functional 247-5i criteria subdivision 251-55 implications 265-68 molecular biology 269, 270 pharmacology 241-73 prejunctional 242, 244 pre- and postjunctional 244, 245 rat anococcygens 246. 247 subdivision 245 Receptors, alpha, adrenergic agonist. uses 270. 271 antagonist uses 271-73 inhibitory. evidence 243 molecular biology 269, 270 pharmacology 241-73 prejunctional 241, 242 pre- and postjunctional 244, 245 subdivision 255 binding studies 257. 258 functional 258-62 implications 265-8 prejunctional 255, 256 Receptor. antiinsulin antibodies 360 Receptors, eicosanoid 3446 classification 37 Receptors, leukotrienes antagonist structure 42, 43 classification. airways 44 functional studies 40 human bronchial muscle 44 ReceDtors. MSH 63-80 maianoma cells 76-79 characterization 78, 79 stimulation 77 U.V. irradiation 77 melanophores 67, 68
Anolis
vii 73-76
forskolin action 75. 76 Xenopus 69-72 photoaffinity labeling 67-80 Receptors, prostanoid antagonists 38 classification, airways 37-39 Saponins. gastrointestinal absorption 431 Sodium tauro-24,25-dihydrofusidate, gastrointestinal absorption 420, 421 Stress anxiety 315 panic attacks 316 Superoxide sources 285. 286 xenobiotic toxicity 286. 287 Superoxide dismutase age effects 290-Y2 distribution 287, 288 aspects 287 genetic inducers 288-90 modulation 288 xenobiotic detoxification 285-91 Surfactant, gastrointestinal absorption 416-18 Swainsonine Wucture 96 Tolbutamine cytochrome P-450 and hydroxylatiun I5@52 interactions 15&53 drug metabolism 147-49 genetic control 149, 150 148 pharmacokinetics pathways 148 Tumor metastases oligosaccharides 85-99 carbohydrate asparagine-linked structure 86-91 lectin binding cells 89. 90 process 85 Tunicamycin metastasis 95, 96 structure 96
Variable receptor affinity hypothesis
Xenobiotic detoxification catalase 297-304 superoxide dismutase 285-92
262, 263
Executive Editors
W. C. Bowman, A. M. Breckenridge and A. C. Sartorelli
PERGAMON
PRESS
OXFORD . NEW YORK . BEIJING . FRANKFURT sAo PAUL0 . SYDNEY . TOKYO . TORONTO
PHARMACOLOGY &THERAPEUTICS Chemotherapy,
Toxicology
and Metabolic Inhibitors
Executive Editor: A. C. Sartorelli Yale University School of Medicine, Department of Pharmacology, New Haven, Connecticut 06510, USA
333 Cedar Street,
Associate Editor: Barbara Z. Renkin, Ph.D. General and Systemic Pharmacology
Executive Editor: W. C. Bowman University of Strathclyde, Department of Physiology & Pharmacology, 204 George Street, Glasgow Gl lXW, Scotland
Clinical Pharmacology
Royal College,
and Therapeutics
Executive Editor: A. M. Breckenridge University of Liverpool, Department of Pharmacology Liverpool L69 3BX, England
& Therapeutics,
P.O. Box 147,
Library Annual Subscription Rates-published in 4 volumes per annum of 3 issues each. Annual Subscription, 1990, DM 2370.00 including postage and insurance, 2 years, 1990/91, DM 4503.00. Specially Reduced Rates fo Individuals: Any individual whose institution takes out a library subscription may purchase a second or additional subscription for personal use at a much reduced rate of DM 740.00 annually. Subscribers to the Journal may claim a 20% discount off Encyclopedia volumes. Prices are subject to change without notice. Subscription enquiries from customers in North America should be sent to Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523, USA, and for the remainder of the world to Pergamon Press plc, Headington Hill Hall, Oxford OX3 OBW, England. At the end of the year, the Subscriber
will receive, free, the annual
subject
index.
It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. By submitting a manuscript, the authors agree that the copyright for their article is transferred to the publisher if and when the article is accepted for publication. However, assignment of copyright is not required from authors who work for organisations which do not Permit such assignment. The copyright covers the exclusive rights to reproduce and distribute the article, including reprints, photographic reproduction, microform or any other reproduction of similar nature and translations. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, electrostatic, magnetic tape, mechanical photocopying recording or otherwise, without permission in writing from the copyright holder.
Photocopying Information for Users in the USA. The Item-Fee Code for this publication indicates that authorization to photocopy items for internal or personal use is granted by the copyright holder for libraries and other users registered with the Copyright Clearance Center (CCC) Transactional Reporting Service provided the stated fee for copying, beyond that permitted by Section 107 or I08 of the United States Copyright Law, is paid. The appropriate remittance of $0.50 per page is paid directly to the Copyright Clearance Center Inc., 27 Congress Street, Salem, MA 01970. Permission for other Use. The copyright promotion, for creating for such copying.
owner’s consent does not extend to copying for general distribution, for new works, or for resale. Specific written permission must be obtained from the publisher
Publishing and Advertising Offices Pergamon Press plc Headington Hill Hall Oxford OX3 OBW England
Pergamon Press Inc. Maxwell House Fait-view Park, Elmsford New York 10523, USA
Volume 44,1989,
Numbers l-3
CONTENTS
PAGE
Number 1 Eicosanoids and airway smooth muscle: P. J. Gardiner Photoaffinity labeling of melanocyte-stimulating hormone receptors: A. N. Eberle, P. N. E. de Graan, T. Scimonelli and F. Solca Asparagine-linked oligosaccharides and tumor metastasis: A4. J. Humphries and K. Olden Inhibitors of DNA gyrase: K. Drlica and S. Coughlin Models and markers used to study cardiac reperfusion injury: J. P. Kehrer and J. W. Starnes
1 63 85 107 123
Number 2 Genetic factors influencing the metabolism of tolbutamide: D. J. Back and M. L’E. Orme Peripheral dopaminergic nerves: C. Bell The uses and limitations of calmodulin antagonists: M. L. Veigl, R. E. Klevit and W. D. Sedwick The pharmacology of (pi- and a,-adrenoceptors: Evidence for and against a further subdivision: J. R. Docherty Superoxide dismutase: Its role in xenobiotic detoxification: A. T. Canada and E. J. Calabrese Catalase: Its role in xenobiotic detoxification: E. J. Calabrese and A. T. Canada
147 157 181 241 285 297
Number 3 Clinical pharmacology of anxiolytics and antidepressants: A psychopharmacological perspective: D. J. Nutt and P. Glue Biological and chemical properties of the hemoregulatory peptide and possibilities for clinical applications: 0. D. Laerum and W. R. Paukovits Immunological aspects of diabetes mellitus: Prospects for pharmacological modification: M. Itoh Intestinal drug absorption enhancement: An overview: E. J. van Hoogdalem, A. G. de Boer and D. D. Breimer Nifedipine: Variability in its kinetics and metabolism in man: D. D. Breimer, J. H. M. Schellens and P. A. Soons
111
309 335 351 407 445
AUTHOR INDEX Back, D. J. 147 Bell, C. 157 Breimer, D. D. 407,445
Kehrer, J. P. Klevit. R. E. Laerum,
Calabrese, E. J. 285,297 Canada, A. T. 285,297 Coughlin, S. 107
Gardiner, Glue. P. Humphries, Itoh, M.
Paukovits,
M. J.
335
309
Olden, K. 85 Orme, M. L’E. W. R.
147 335
Schellens, J. H. M. 445 Scimonelli, T. 63 Sedwick, W. D. 181 Solca, F. 63 Soons, P. A. 445 Starnes, J. W. 123
63
P. J. 309
0. D.
Nutt, D. J.
de Boer, A. G. 407 de Graan, P. N. E. 63 Docherty, J. R. 241 Drlica, K. 107 Eberle. A. N.
123 181
1
85 van Hoogdalem, E. J. Veigl, M. L. 181
351
iv
407
SUBJECT INDEX Absorption enhancement, intestinal drugs 407-33 Adenylate cyclase, a,-adrenoceptors 266-68 Ageing a-adrenoceptor responsiveness 268 catalase 303, 304 superoxide dismutase activity 290-92 Airway smooth muscle eicosanoid action 4651 AMP 49, 50 calcium 47-49 inositol phospholipid 50 and eicosanoids l-52 biosynthesis 2-4 biosynthetic scheme 3 hyperactivity and eicosanoids 32-35 isolated and eicosanoids 7-36 cat 18, 19 dog 19-21 guinea pig 8-12 human 22-31 monkey 21,22 rat 16, 17 metabolism 4-7 uptake 4 Antidepressants anxiety 318-22 clinical pharmacology 309-27 mechanism and noradrenergic function 324, 325 Anxiety benzodiazepines 317 and depresssion relationship 312-14 diagnostic classification 309-11 tricyclic antidepressants 322, 323 Anxiolytics, clinical pharmacology 309-27 Asparagine-linked oligosaccharides, tumor metastases 85-99 Asthmatics, leukotiienes and airways in man 30, 31 Autoantibodies, serum in diabetes 355-61 Autoimmunity 352, 353 Azone, gastrointestinal absorption enhancement 429,430
drug target 187 nuclear magnetic resonance 207-10 -regulated enzymes 183-87 spectroscopic studies 204-207 structure 181, 182 structure-function probes 203-l 1 Calmodulin antagonists 181-229 anticancer agents 218, 219 binding properties 196-99 calmodulin activity 212-14 DNA interactive drug modification 219-25 bleomycin 221, 223, 224 DNA repair 222-24 hydrophobic 200-202 inhibitory properties 196-99 neuroleptic drugs 217, 218 peptides 203 pharmacodynamics 214-17 pleiotropic drug resistance 225-28 structure 188-95 therapeutic uses 214-19 types 187 Cardiac reperfusion injury age 132-34 cell culture 126, 127 definition 123, 124 hypoxia 130, 131 in vitro 126-30 markers 125 experimental 135-38 mechanisms 138 models 124, 126 pathways 139, 140 perfused preparation 128-30 Purkinje fiber 127, 128 Carnitine derivatives and gastrointestinal absorption 430 Castanospermine structure 96 Catalase age effects 303, 304 disease 299 genetics 298 inducers 299, 300 inhibition 300, 301 peroxisome 301 species variability 302, 303 toxicology 298 xenobiotic detoxification 297-304 Clomipramine, panic patients 320 Coumarins DNA replication 108 DNA supercooling 108 eukaryotic effects 109, 110 Cyclosporin, diabetes prevention 377-79 Cytoskeleton and calmodulin 183
Benzodiazepines, anxiety 317, 318 Bile salts, gastrointestinal absorption enhancement 418-20 Calcium a-adrenoceptors 265, 266 hypoxia and ischaemia markers 137, 138 Calcium binding agents, gastrointestinal absorption enhancement 427, 428 Calmodulin activities and antagonists 212-14 antagonist specificity 210, 211 circular dichroism 207 drug binding sites 201
Depression anxiety coexistence 313, 314 diagnostic classification 311-13 pharmacology 316 V
vi
SUBJECT INDEX
Diabetes, a-adrenoceptor responsiveness 269 Diabetes mellitus autoantibodies 355-61 anti-insulin 358 islet cell cytoplasmic 355-57 islet cell surface 357, 358 HLA-D region 353-55 immune complexes 361, 362 immunological aspects 351-82 DNA damage alkylating agent toxicity 224, 225 calmodulin inhibitors 221-25 DNA gyrase inhibitors 107-16 bacterial cell sensitivity factors 114 cell death 114 lesion repair 113 mutations and survival 115, 116 Dopaminergic neurons, peripheral 157-75 biochemical features 158-60 distribution 16675 gastrointestinal 172, 173 kidney 166-71 lung 173, 174 reproductive 173 histochemical features 160-63 identification 157-66 pathway 158 pharmacological features 164-66 ultrastructural features 163, 164 Drug interactions, tolbutamine metabolism I50-53 Eicosanoids, airway smooth muscle l-52 Enamines, gastrointestinal absorption 424, 425 Fatty acids, gastrointestinal
absorption
421, 422
Gastrointestinal drug absorption 407409 barriers 409-I 1 enhancers 41 l-32 structure 407409 Glycerides, gastrointestinal absorption 422-24 Glycoprotein processing, metastatic cells 86-88
Hemoregulators, peptide 335-46 chemical properties 336 clinical applications 345, 346 history 335, 336 monomer-dimer regulatory system properties 339-%2 purification 337
342-44
Imipramine, panic attacks 319 Immune complexes in diabetes 361, 362 Inhibitors DNA gyrase 107-16 metastatic 94-99 Insulin-dependent diabetes mellitus (IDDM) animal models 369-77 NOD mouse 375, 376 NZB mouse 376, 377 spontaneous 372-75 streptozotocin 369-71 free radical scavengers 38&82 immunosuppression 379, 380
lymphocyte reconstitution 379 prevention 377-82 Insulitis antiimmune responses 363 killer cells 367, 368 lymphocyte function 368 macrophages 366 T lymphocytes 36466 Kidney, dopaminergic neurons function 167-70 pathophysiology 171, 172
166-72
Lectin-resistant mutants, metastatic potential 91-94 Leukotrienes airways smooth muscle hyperactivity 35, 36 guinea pig airways smooth muscle 12-15 human isolated smooth muscle 27-30 metabolism 6, 7 rat isolated smooth muscle 17 therapeutic uses 52 Liposomes, gastrointestinal absorption 428, 429 Malignancy markers 90 Melanocyte stimulating hormone (MSH) features 63, 65 photoaffinity labels 65 biological activity 67 derivatives 66 structures 64 Melanophores, U.V. irradiation 68, 69 apparatus 69 Metastases see also tumor metastases functional defects 93, 94 glycoprotein processing inhibitors 94-99 lectin-resistant mutants 91-94 Mixed micelles, gastrointestinal absorption 425-427 Models cardiac reperfusion injury 124, 126 diabetes 369-77 Monoamine oxidase inhibitors, panic attacks 320, 321 Multipotent stem cells 340 Myelopoietic progenitor cells 339, 340
Nifedipine area under curve 448, 449 biotransformation 446 excretion 447 pharmacokinetics 449 population studies 445-50 variability in disposition kinetics 450-52 Non-steroidal anti-inflammatory drugs, gastrointestinal absorption 413-16 Nuclear magnetic resonance, calmodulin 207-10
Panic attacks 316, 319, 320 combination pharmacotherapy 321 psychological treatment 325, 326 Phenothiazines, gastrointestinal absorption 428 Photoafflnity labeling, MSH receptors 63-80 melanoma cells 76-79 melanophores 67-76
SUBJECI- INDEX Polyacrylic acid, gastrointestinal absorption enhancement 431. 432 Prostanoids see alsomuscle eicosanoids airways smooth 1. 2 therapeutic uses 51, 52 Protein kinases and calmodulin
184
Quinolones bacterial DNA 110,111 1I1 DNA supercooling DNA synthesis inhibition
112
Receptors. alpha, adrenergic agonist. therapeutic uses 270, 271 antagonist uses 271-73 functional 247-5i criteria subdivision 251-55 implications 265-68 molecular biology 269, 270 pharmacology 241-73 prejunctional 242, 244 pre- and postjunctional 244, 245 rat anococcygens 246. 247 subdivision 245 Receptors, alpha, adrenergic agonist. uses 270. 271 antagonist uses 271-73 inhibitory. evidence 243 molecular biology 269, 270 pharmacology 241-73 prejunctional 241, 242 pre- and postjunctional 244, 245 subdivision 255 binding studies 257. 258 functional 258-62 implications 265-8 prejunctional 255, 256 Receptor. antiinsulin antibodies 360 Receptors, eicosanoid 3446 classification 37 Receptors, leukotrienes antagonist structure 42, 43 classification. airways 44 functional studies 40 human bronchial muscle 44 ReceDtors. MSH 63-80 maianoma cells 76-79 characterization 78, 79 stimulation 77 U.V. irradiation 77 melanophores 67, 68
Anolis
vii 73-76
forskolin action 75. 76 Xenopus 69-72 photoaffinity labeling 67-80 Receptors, prostanoid antagonists 38 classification, airways 37-39 Saponins. gastrointestinal absorption 431 Sodium tauro-24,25-dihydrofusidate, gastrointestinal absorption 420, 421 Stress anxiety 315 panic attacks 316 Superoxide sources 285. 286 xenobiotic toxicity 286. 287 Superoxide dismutase age effects 290-Y2 distribution 287, 288 aspects 287 genetic inducers 288-90 modulation 288 xenobiotic detoxification 285-91 Surfactant, gastrointestinal absorption 416-18 Swainsonine Wucture 96 Tolbutamine cytochrome P-450 and hydroxylatiun I5@52 interactions 15&53 drug metabolism 147-49 genetic control 149, 150 148 pharmacokinetics pathways 148 Tumor metastases oligosaccharides 85-99 carbohydrate asparagine-linked structure 86-91 lectin binding cells 89. 90 process 85 Tunicamycin metastasis 95, 96 structure 96
Variable receptor affinity hypothesis
Xenobiotic detoxification catalase 297-304 superoxide dismutase 285-92
262, 263