Table Of ContentIUPHAR 9TH INTERNATIONAL
CONGRESS OF PHARMACOLOGY
LONDON 1984
PROCEEDINGS
IUPHAR 9TH INTERNATIONAL
CONGRESS OF PHARMACOLOGY
LONDON 1984
Under the Patronage of HRH The Duke of Edinburgh RG KT
Sponsored by
International Union of Pharmacology; British Pharmacological Society;
The Royal Society
PROCEEDINGS
VOLUME 3
EDITORS
Professor Sir William Paton
Professor James Mitchell
Professor Paul Turner
Assistant Editors
Cheryl Padgham
Eileen Ashcroft
© The Macmillan PressLimited 1984
Softcoverreprintofthehardcover 1stedition 1984
All rights reserved. No reproduction, copy or transmissionofthis publicationmay be
madewithoutwrittenpermission.
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1956(as amended).
Any personwho does any unauthorised act in relationto this publicationmay be
liable to criminalprosecution and civilclaimsfor damages.
First published 1984
Publishedby
Scientific& Medical Division
THE MACMILLAN PRESS LTD
Houndmills, Basingstoke, Hampshire RG21 2XS
and London
Companies and representatives
throughouttheworld
ISBN978-0-333-37136-7 ISBN978-1-349-17615-1 (eBook)
DOI 10.1007/978-1-349-17615-1
IUPHAR 9th INTERNATIONAL CONGRESS OF
PHARMACOLOGY
LONDON 1984
INVITED PROGRAMME
VolumeOne
Monday 30July
Invited Lectures
L1 Localisationoffunctional activityinthe central nervoussystem
bymetabolic probes L. Sokoloff
L2 Pharmacologicalapproaches to neuropeptidefunction-
SubstanceP L.L. Iversen
L3 Neglectoffunction andobsessionwithstructureintoxicity
testing G. Zbinden
U Receptorlocalisationinasymmetriccells A.W. Cuthbert
L5 TheWitheringCommemorationLecture D. Noble
Symposia Papers
S1 Modificationand turnoverofreceptors 1,3,5.
S2 Beta-Iactamantibioticswithnovelnuclei 1-3,5,6.
S3 Antiplateletand antithromboticdrugs 7.
S4 Mechanismsofactionofsmooth musclerelaxants 1,3,4, 6, 8,9.
S5 Insulinandinsulin-likegrowthfactors, receptors andmediators 2.
S6 Tissueselectivetoxicity 1,2,3,5.
Tuesday31July
Invited Lectures
L6 Molecularpharmacologyofsodiumchannelofmammalian
brain W.A. Catterall
L8 Dopaminergic nerves C. Bell
L9 Theproblems ofextrapolatinglaboratorydata tomanin
teratology R. Jelinek
Symposia Papers
S7 Regulation ofadenylate cyclase 2-6.
S8 Antiviraldrugs 3-4,6-9.
S9 Painmechanisms 1-6.
VolumeTwo
S10 Cardiacinotropic agents 1,5,8.
S11 PhospholipaseA inhibitors 1,2,6,7,9.
2
S12 Repair andpromotioninchemicalcarcinogenesis
v
Wednesday 1August
InvitedLectures
L12 Therole ofadrenalineinessentialhypertensioninman M.J. Brown
L13 Glutathioneand tissuetoxicity S.Orrenius
Symposia Papers
S13 Analysisofdrug mechanismsbysingleionchannel recording 1.
S14 Modemapproachestodrugdesign 1-4.
S15 Novelantihypertensivedrugs 1-4,7.
S16 Peptide effectors and modulatorsofsecretion 1-6.
S17 Amine oxidaseenzymesand their inhibition 1-3,5,7-8.
S18 Cellularinjury caused byfree radicals 2-6.
Thursday2August
InvitedLectures
L14 Neuropeptideprecursorsandacetylcholinereceptor: molecular
structuresand geneexpression S.Numa
L15 Cancerchemotherapy: Examples ofcurrentprogressandfuture
perspectives R.E. Handschumacher
L16 Receptorsfor thromboxanesandprostaglandins R.L. Jones
L17 Activation ofcalmodulin bymetalcations andoccupancyofits
metal bindingsites W.Y. Cheung
Symposia Papers
S19 Drugs actingthroughcalciumchannels 4,5,7,8.
S20 Newstrategies inanti-parasitic chemotherapy 1-7.
VolumeThree
S21 Endogenousprostanoidsinman 2-6.
S22 Leukotrienesand otherlipoxygenaseproducts 1-6.
S23 Steroid receptors 2,3,5,7.
S24 Modesofaction ofantidepressive drugs 1,3-7.
Friday3August
InvitedLectures
L21 Generationofdrug resistance bygene amplification R.T. Schimke
Symposia Papers
S25 GABAreceptors 2-4,6-8.
S26 Multipleformsofdrugmetabolisingenzymes 1-6.
S27 Salvageofthe ischaemicmyocardium 1,5-7.
S28 Peptides asdrugs 2-5.
S29 Interleukinsand othercytokines 1-3, 5,7.
S30 Gastrointestinalmucosalprotection 2-7.
vi
CONTENTS OF VOLUME THREE
Page
Symposium21 Endogenous prostanoidsin man
Vascular and plateleteffects ofprostacyclin and prostaglandinD in man
2
C.T. Dollery, S.E. Barrow, D. Heavey and J.M. Ritter 3
Prostacyclin and cerebral.circulation
E.S. Gabrielian and S.E. Akopov 7
Effect ofprostanoidson the coronarycirculation
A. Wennmalm, A. Edlund, L. Kaijser and C. Patrono 13
Effects of aspirin and dazoxiben upon the peripheralcirculation inman
A.J. Cowleyand S. Heptinstall 21
Controlledtrials on the effects ofprostacyclin invascular disease
R.J. Gryglewski 29
Symposium22 Leukotrienesand otherIipoxygenaseproducts
Leukotriene~: mechanism offormation and enzymatic hydrolysis
O. Radmark, T. Shimizuand B. Samuelsson 39
Formation and mechanism of action ofleukotrienes: enzymatic hydration
ofleukotriene~ byhuman blood cells
F.A. Fitzpatrick, W.F. Liggett and J.E. McGee 43
Pharmacological studies on the release and effectsofleukotrienesin
human and guinea piglung tissue
G.C. Folco 49
Substrate and regulatoryfunctions ofeicosapentaenoicand
docosahexaenoicacidsfor the 5-lipoxygenasepathway
T.H. Lee, J.M. Drazen, R.A. Lewisand K.F. Austen 55
Actions ofleukotrienesinthe circulation
P.J. Piper, A.W.B. Stanton, L.J. Mcleod, S.A. Gatton and L.G. Letts 63
LeukotrieneB4: amediatorof leucocyte function
AW . Ford-Hutchinson 69
Symposium23 Steroid receptors
Biologicaland clinicalaspects ofoestrogenreceptormeasurementsin
rapidlyprogressing breastcancer
R.I. Nicholson, D.W. Wilson, G. Richards, K. Griffiths, M. Williams,
C.W. Elston and R.W. Blarney 75
Unexpectedoestrogenicactivityin aderivative of antioestrogenic
triphenylethylenes
V.C. Jordan, R. Koch, M.E. Lieberman and S. Mittal 81
The regulationofthe biologicalfunction ofsteroid-receptorsinchickens
and humans
T.C. Spelsberg, B.A. Littlefield, P.A. Boyd-Leinen, O.L. Kon,
G. Martin-Dani, B. Gosse, K. Rasmussen, J. Horaand A. Goldberger 85
Phosphorylationofthe glucorticoid receptor
W.B. Pratt, P.R. Housley, M.K. Dahmerand J.F. Grippo 93
Symposium24 Modesofaction ofantidepressive drugs
Neurochemical and molecularstudies of antidepressant effectsin the
modelled depression in animals
A.V. Valdman, V.V. Rozhanet, N.A. Avdulov, M.M. Kozlovskaya
and V.P. Poshivalov 103
vii
Page
Regulationof 5-hydroxytryptamine (5-HT) uptake: endocoidmodulators
and the actionof imipramine
E. Costa andM.L. Barbaccia 109
~-Adrenoceptor agonists, ECTandotherantidepressants: effects on
serotoninbiochemistryandfunction
A.R. Green, V.L. Nimgaonkar and G.M. Goodwin 117
Central~-adrenoceptorregulation and adaptationunderphysiologicaland
pathophysiologicalconditions
F. Sulser, D.O. Gillespie and O.H. Manier 125
a2-Adrenoceptors and antidepressanttreatments
C.B. Smithand P.J. Hollingsworth 131
Mechanism of actionof antidepressantdrugs given repeatedly: changesin
the responsesmediated by noradrenaline (at) and dopamine receptors
J. Maj 137
Friday Invited Lecture
The acquisition of methotrexateresistance by gene amplification
R.T. Schimke, S. Beverley, R. Cassin, H. Diddens, R. Johnston,
A. Hill, B. Mariani, H. Rath andT. Tlsty 147
Symposium2S GADAreceptors
Electrophysiologyof GABA receptorsin thevertebratecentralnervous
system
R.A. Nicoll and N.R. Newberry 153
Bicuculline-insensitive GABA receptors
B
N.G. Bowery, A.L. Hudson, O.R. Hill and G.W. Price 159
Purification and properties of the GABNbenzodiazepine/barbiturate
receptorproteinfrom rat brain
R.W. Olsen, J.B. Fischer, G.B. Stauber, R.G. King and
J. Yang-Ransom 171
GABA receptors and related bindingsites
G.A.R. Johnston, R.D. Allan, A.D. Benton, S. Chen Chow,
C.A. Drew, B.P. Hiern, G. Holan, R. Kazlauskas, H. Rzezniczak
and R.P. Weatherby 179
GABA receptors: Clinicalimplications
S.J. Enna 185
GABAreceptors- Co-Chairman'sconcludingremarks
K.S. Rayevsky 193
Symposium26 Multipleforms ofdrugmetabolisingenzymes
Characterizationof the multiplicityof drug-metabolizingenzymes
observationson cytochromeP-450 diversity
E.F. Johnson, M.J. Finlayson, J. Raucy and R.H. Tukey 197
Multiplicityandfunctional diversity of rat hepaticmicrosomalcytochrome
P450isozymes
W. Levin, P.E. Thomas, L.M. Reik, A.W. Wood andD.E. Ryan 203
Multiplicityof cytochrome P450 and its genestructure
Y. Fujii-Kuriyama, K. Sogawa, Y. Suwa, K. Kawajiri and O. Gotoh 211
Tissue and cellulardifferencesin theexpressionof cytochrome P450
isozymes
B.A. Domin, C.J. Serabjit-Singh, R.R. Vanderslice, T.R. Devereux,
J.R. Fouts, J.R. Bend and R.M. Philpot 219
viii
Page
Species and tissue differences inthe occurrenceofisoenzymes of
glutathione transferase
B. Mannervik, C. Guthenberg, H. Jensson, M.K. Tahir,
M. Warholm and P. Alin 225
Multiple forms of epoxide hydrolase
C. Timms, F. Oesch, L. Schladt and W. Worner 231
Symposium 27 Salvageofthe ischaemic myocardium
Therapeuticinfarctsize reduction
D.J. Hearse and D.M. Yellon 241
Is drug inducedreductionof the infarctsizeessentialfor protection
against suddencoronarydeath?
L. Szekeres, M. Koltai and I. Lepran 247
Myocardial salvage bypharmacologicalinterventions
D.M. Yellon, D.J. Hearse and J.M. Downey 251
Evidencefor myocardial salvage inhuman clinicalischaemia
P.G. Hugenholtz, J.W. Deckers, W.J. van der Giessen, P.S. Serruys
and J. Lubsen 257
Symposium28 Peptidesas drugs
Approaches to the rationaldesign ofpeptide analoguesfor use intherapy
D.F. Veber 271
Metabolism ofenkephalinsand itsinhibition
J.C. Schwartz, B. Giros, C. Gros, C. Llorens and B. Malfroy 277
SubstanceP antagonists as a new type of drug
S. Rosell 283
ACTH-like neuropeptides aspotentialpsychoactive and neuroactive
drugs
D. de Wied 287
Symposium29 Interleukins and othercytokines
Interleukin2and otherimmunoregulatoryT celllymphokines: biological
significance
A.L. de Weck, B. Stadler, F. Kristensen, F. Bettens, F. Joncourt
and C. Walker 295
Interleukin- 1:An Overview
L.J. Rosenwasser 301
Differentimmunosuppressive activity of equimolardoses ofprednisolone
prodrugs
B.M. Frey, C. Walker, F.J. Freyand A.L. de Weck 307
Lymphokinesthatmediateinflammation
R.E. Rocklin 311
The role oflymphokines and cytokinesin tumordevelopmentand
surveillance
B.M. Vose and V.E. Moore 323
Symposium30 Gastrointestinalmucosal protection
Clinicalaspects of gastric protection
S.J. Konturek 341
Biosynthesis ofendogenous arachidonate productsinvolved ingastric
damage and protection
B.J.R. Whittle and N.K. Boughton-Smith 345
ix
Page
Mechanismsofcytoprotection
A. Robert 355
Morphological and tropic actions ofprostandoidson the gastrointestinal
mucosa
F. Halter 361
Cellular aspects ofmucosal damage and protection
K-Fr. Sewingand U. Weissenborn 367
The mucusand bicarbonatebarrieringastroduodenaldefence
A. Allen and A. Garner 373
Index 383
x
