Co-Transmission: Proceedings of a Symposium held at Oxford during the 50th Anniversary Meeting of the British Pharmacological Society

267 Pages·1982·33.8 MB·English

by  A. C. Cuello (eds.)

CO-TRANSMISSION
CO-TRANSMISSION
Proceedings of a Symposium held at Oxford during
the 50th Anniversary Meeting of the British
Pharmacological Society
Edited by
A.C.CUELLO
University Department ofPharmacology,
Oxford
M
©The Contributors
Softcoverreprint ofthe hardcoverIstedition 1982
Allrights reserved. No part ofthis publicationmay be reproduced or transmitted
inany form or by any means,without permission.
Firstpublished1982 by
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ISBN 978-1-349-06241-6 ISBN 978-1-349-06239-3(eBook)
DOI 10.1007/978-1-349-06239-3
Contents
Foreword vii
Preface xi
1. Coexistenceof traditional neurotransmitters with peptides inthe
mammalianbrain:5-hydroxytryptamineand substance Pinthe
raphe and 'Y-aminobutryricacidand motilin inthe cerebellum.
Victoria Chan-Palay.
2. Coexistenceof putative neuromodulatorsinthe sameaxon:
pharmacologicalconsequences at receptors.E.Costa. 25
3. Neuronalcoexistence of putativetransmittersinthe spinalcord and
brainstem of the rat.R. F.T.Gilbert, P.C.Emson,S.Hunt,G.W.
Bennett and C.A.Marsden. 51
4. Coexistenceofclassicaltransmittersand peptides inneurones.
T.Hokfelt, J. M.Lundberg, L.Skirboll,O.Johansson,M.Shultzberg
and S.R.Vincent. 77
5. Theadrenal medulla:amodel for studying synthesis, co-storageand
co-secretionof peptides and catecholamines.O.Humberto Viveros
and StevenP.Wilson 127
6. Theco-transmitterhypothesis,with specialreference to the storage
and releaseof ATPwith noradrenaline and acetylcholine.
G.Burnstock. 151
7. Coexistenceofneuroactive substancesasrevealedbyimmunohisto
chemistry with monoclonal antibodies.J. V.Priestleyand A.C.
Cuello. 165
8. Coexistenceof monoamines in peripheral adrenergicneurons.
GuillaermoJaim-Etchevery and LuisMariaZieher. 189
9. Coexistenceof neurotransmittersubstancesinaspecifically
defined invertebrate neurone.Neville N.Osborne. 207
10. The diffuseneuroendocrinesystem:an extension of the APUD
concept.A.G.E.Pearse. 223
11. Neuropharmacological and neurophysiological consequences of the
co-releaseof neurotransmitters.R.W.Ryall. 235
12. Coexistenceofadenosine 5'-triphosphateinacetylcholineinthe
electomotorsynapse.H.Zimmermann. 243
Index 261
v
Foreword
It is a pleasure to be asked to write a foreword to this volume, based on the
symposium at the 50th Anniversary meeting of the British Pharmacological
Society at Oxford, that wasbrought into being by the imagination and energy
of mycolleague,ClaudioCuello.Itisparticularlystimulating for one brought up
scientifically in Dale's old laboratory, who remembers the period when neuro
transmission byone transmitter,let aloneseveral,wasnot accepted and whowas
present whenJ. C.Eccles,at a Royal Society meeting,announcedhisconversion.
Almostimmediately,inthe contextof the intenseinterest incentral transmission
that Eccleshad aroused, the idea that one neurone could releasebothan inhibi
tory and an excitatory transmitter wascanvassed,but found to be unnecessary
with the recognition ofinterpolatedinhibitoryinterneurones.From then on the
issue was not ofmultiple transmitters, but of being able to identify any trans
mitterasavalidcandidate for eachofthe variousdistinguishablecentralsynaptic
mechanisms- abattlethat isstillnot finished. Therehavebeen manysubsequent
additions to our knowledge: the recognition ofpresynapticinhibitory processes,
allowing a modulation of postsynaptic effect through the control by the trans
mitter from one nerve terminal of the transmitter output from a second - a
biochemically more economical processthan the two transmittersfightingit out
postsynaptically; the extension of this to negative feedback by a transmitter
onto its own terminals;the possibilitiesofcontrolof receptorfunction (up'and
'down' regulation) according to exposure to transmitter. Together with the
delicatecentral controlofresponsethroughthe frequency ofdischargedown the
nerve fibres, mediated by reflexes drawing on all the subtle connectivity of the
central nervoussystem, the availablemechanismsseemedto offer amplescopeto
allow physiologicalfunction to beaccuratelyadjusted to any physiologicalneed.
A general conceptualrequirement for the additionalcontrolmechanismsoffered
by co-transmission could hardly be said to have existed; and if there has been
resistance to the idea, perhapsit wasmore on grounds ofeconomy ofhypothesis
than anythingelse.
Thus it seems to me not only wrong when 'Dale's principle' is cited in the
terms of 'one neurone-one transmitter') as though an established functional co
transmissionwouldfalsifysomeruleenunciated byhim,but alsotomissone of his
creative insights.If one goes back to what he wrote in the Nothnagellecture,or
tohistalks at the Royal Society andlater to the studentsofSt. Andrewsin1952,
the issueisadifferent one.Hebroughtthe newknowledgeaboutcholinergicand
vii
adrenergictransmissionintorelation with old work on cross-innervation, pointing
out how the latter could now be 'summarized by stating that any cholinergic
fibre willfunctionallyreplaceanyothercholinergicfibre, and thatany adrenergic
fibre willreplaceanyadrenergicfibre, but that neithercanassumethe function of
the other'.Thesephenomenaappeared 'to indicate that the natureofthe chemi
cal function, whethercholinergicor adrenergic,ischaracteristicfor eachparticu
lar neurone and unchangeable'. To this he added the past work on antidromic
vasodilatation,brought againinto prominence by SirThomas Lewis'sdemonstra
tion that the 'flare' evoked by histamine in skin was due to an axone reflex in
sensory nerves. Was it possible that discovery and identification of a chemical
transmitter of axon-reflex vasodilatation would provide a clue to the central
transmission process? He wassuggestingnot aparticular number oftransmitters,
but what might be called a 'principle of biochemical consistency' within a
neurone, that might bring with it the great prize ofa wayto identifythe trans
mitter at the first sensory synapse. Dr W. Feldberg has reminded me of Dale's
letter to him (recently published in Notes and Recordsof the Royal Society 30
231, 1976) written during the preparation of the Nothnagel lecture, which is
worthtranscribing.
4th September,1934
Mydear Feldberg,
Iwasverygladto hear from you,and to hearthat you and
your familyare enjoying Cornwall.Readingbetween the lines,
Iamsorry to getthe impression that you arenot havingthe
bestofweather.Asamatteroffact,however,the English
coast and countrylook at their best and most characteristic
whenthe fineweatherisbroken by rainstorms.
Iam verygrateful to you for your trouble,and the progress
whichyou aremaking with my Nothnagel Lecture.Ifyou
would liketo sendmewhat you havealready done,by post,I
should getitjust intime to take with meto America;and I
might usethe returnjourneyto familiarisemyselfwith it a
little,and mark any points for discussion.However,that isa
matterwhich Iwould gladlyleaveentirelyto your judgment.
Ifyou would prefer to retain the wholeofthe MSuntil your
translationiscompleted,by allmeansdoso.Youmight then,
whenyou return,consult Mrs.Cutts about the possibility of
gettingsomeofit,at least, into typescript before Ireturn.
There isone point which Ipropose to add at the end, even
ifit involvessacrificingsomeearlierpassages.Allthe evidence
seemsto point to chemicalfunction beingacharacteristicof
nervefibre, or, perhaps,ofthe cellfrom whichitoriginates.A
viii
fibrearisingfrom asympatheticganglioncellappears to be
adrenergic,and to beincapable ofchangingits function.Think
ingon those lines,it seemsto me that there isagood dealof
probabilitythat chemical transmission ofantidromic vaso
dilatationat the peripheralend ofasensory neurone might be
expected tousethesamesusbtanceastransmission ofasensory
impulse to a motorcellat acentralsynapse. Itis,ofcourse,
merely aguess,butit isa point ofsomeinterest,Ithink and
one worthmentioninginalecture.It would beextremely
interestingifidentificationofthe chemical transmitter for
antidromic vasodilatationshould lead directly to the problem
ofchemical transmissionin the centralnervous system.How
ever,Ican think what isappropriate to sayon that point,if
anything,when Ireturnfrom America. Iamgladyouare taking
afullholiday,and gettingfit for agood winter's work.
Yours verysincerely,
H.H.Dale
Today, Sir Henry might well demand evidence as cogent as that which he
and his colleagues put forward for cholinergic transmission,beforeaccepting co
transmission; yet one cannot believehe would objectin principle.Indeed,ifone
reads another letterto Feldberg in 1962 inthe samecollection,wherehe puzzles
over the functional vasodilatationofthe salivarygland,it seemsmore likely that
he would have been delighted at the new evidence about VIPand at the combi
nationofhistochemicaland physiological experimentbehindit.
Yet perhaps he would also come back to the question, with all the new evi
dencethis volumepresents,ofthe 'characteristicchemical function'ofaneurone.
Isit possible that it islessunchangeable thanhe suggestedand that the selective
repression of the genetic capacity to synthesize all known and unknown trans
mitters in each cell is not always complete, or immutable? Consideringthe pre
sentknowledge ofthe ultrastructureofthe neurone,isit possiblethat differential
release might indeed take place, between (say) release from the dendrites, with
short supply lines, compared with release at nerveterminalsat the end ofalong
axone? Could re-innervation experiments help to disentangle the biochemically
consistent from the biochemically mutable functions ofthe neurone? Howdoes
it come about that the most commonly chosen partners in the neurochemical
dance seemto beadrenalineand the enkephalins?
Perhaps it is not unfitting to think ofhim readingand discussingthis volume,
unruffled by some mentions ofhis name,as searching aseverinhisquestioning
ofthe experimenters,but aseagerasthey to seewhere the newwork wouldlead.
w.
D.M.Paton
ix
Preface
The committee organising the celebratory meeting ofthe 50th Anniversary of
the foundation ofthe British Pharmacological Society consideredit appropriate
to include a main symposium on an emerging subject in pharmacology. Co
transmission could not be a more appropriate problem,asthe possibleexistence
of multiple transmitters in single neurones can profoundly change our under
standing of the pharmacology of central and peripheral nervous systems. This
book represents a collection of papers from distinguished colleagues who have
made great contributions to the development ofthis idea, many ofwhom have
strong links with the Society. Some ofthe contributions were presentedwithin
the frame ofthe meeting,whileotherswereinvited papers.
I am most grateful to the authors for their co-operation towards the speedy
publication of this volume and for accepting minor editorial changes. I would
also like to acknowledge the enthusiastic co-operation receivedfrom Macmillan
Press for both the meeting and the publicationofthis book.Inthis connection,
I would particularly like to acknowledge the personal interest ofMrAlexander
Macmillan on the successofthe meeting and to thank Dr Sharrockand MrHarry
Holt for their enthusiastic contribution to the efficient productionofthe book.
Thesecretarial assistance ofEllaIleswasinvaluable,dealingwithcorrespondence,
editing references and indexing.
From Oxford I would like to express my gratitude to Professor Sir William
D. M.Paton and Dr Richard Green for their direct involvement inthe material
isation of the Symposium, and The Rector and Bursar of lincoln Collegefor
their help in lodging our guests and for offering a home for social events. The
celebration of the 50th Anniversary of the Society and the Co-transmission
symposium at Lincoln College were particularly pleasant events, as we were
distinguished by the presence of honorary members of the Society such as
Professors Blaschko, Biilbring, Feldberg, Kosterlitz, Paton and Vogt, together
with many eminentcolleagues.
Finally, I would also like to thank my wife, Martha, for her support in this
endeavour.
A.C.C.
xi
1
Coexistence of traditional
neurotransmitters with peptides in the
mammalian brain: 5-hydroxytryptamine
and substance P in the raphe and
-y-amlnobutyrlc acid and motilin in the
cerebellum
Victoria Chan-Palay(Departmentof Neurobiology, The HarvardMedicalSchool,
Boston,Massachusetts02115,USA)
INTRODUCTION
This chapter will deal with two examples of the coexistence ofneuroactive sub
stances in single neurones of the mammalian central nervous system: first,the
5-hydroxytryptamine (5-HT; serotonin)-containing neurone in the raphe and
other brain stem nuclei that have coexistent substance P;second, the 'Y-amino
butyric acid (GABA)-containing Purkinje neurones of the cerebellum which
havecoexistentmotilin.
In the context to be discussedhere,coexistence denotes asituationin which
more than one neuroactive substance canbelocalisedby cytochemicalmeansin
an individual neurone. Usuallythis has meant the combination ofa traditional
neurotransmitter,suchasacetylcholine(ACh)ornoradrenaline(NA)oranamino
acid, together with apeptide,suchassubstance Porenkephalin.Thisdefinition,
however, doesnotexclude the presenceofmore than one traditionalneurotrans
mitter inthe samecellor more than oneneuroactive substance,suchaspeptides.
The issue of the presence of multiple neuroactive substances in neurones isnot