Molecular Action of Insecticides on Ion Channels

345 Pages·1995·2.53 MB·English

by  J. Marshall Clark (Eds.)

ACS SYMPOSIUM SERIES 591
Molecular Action of Insecticides
on Ion Channels
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059 J. Marshall Clark, EDITOR
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9 University of Massachusetts
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cs.99
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12 | http://pun Date: May Devbeylo tpheed D frivoimsio an s yomf Apgorsioucmhe mspiocanlsso red
2, 20catio at the 207th National Meeting
uly 2Publi of the American Chemical Society,
J San Diego, California,
March 13-17, 1994
American Chemical Society, Washington, DC 1995
In Molecular Action of Insecticides on Ion Channels; Clark, J.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1995.
QP 801 .I48M65 1995 copy 1
Molecular action of
insecticides on ion
Library of Congress Cataloging-in-Publication Data
Molecular action of insecticides on ion channels / J. Marshall Clark,
editor.
p. cm.—(ACS symposium series; 591)
"Developed from a symposium sponsored by the Division of Agro­
-chemicals at the 207th National Meeting of the American Chemical
Society, San Diego, California, March 13-17, 1994."
1
0
w0 Includes bibliographical references and index.
1.f
9 ISBN 0-8412-3165-6
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95- 1. Insecticides—Physiological effect—Congresses. 2. Ion channels—
19 Congresses. I. Clark, J. Marshall (John Marshall), 1949 - .
k- II. American Chemical Society. Division of Agrochemicals. ΙΠ. Amer­
1/b ican Chemical Society. Meeting (207th: 1994: San Diego, Calif.)
2 IV. Series.
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1 QP801.I48M65 1995
oi: 574.87'5-4c20 95-6612
org 5 | d CIP
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12 | http://pun Date: May TChopisy briogohkt ©is p1r9i9n5te d on acid-free, recycled paper.
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2, 2cati American Chemical Society
uly 2Publi Achlla pRteigrh itns tRhiess evrovleudm. eT inhdei caaptepse atrhaen cceo poyfr igthhet ocwodneer 'ast c tohnes ebnott tthoamt roefp rtohger afpirhsitc pcaogpeie so fo fe athche
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PRINTED IN THE UNITED STATES OF AMERICA
In Molecular Action of Insecticides on Ion Channels; Clark, J.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1995.
1995 Advisory Board
ACS Symposium Series
M. Joan Comstock, Series Editor
Robert J. Alaimo Cynthia A. Maryanoff
Procter & Gamble Pharmaceuticals R. W. Johnson Pharmaceutical
Research Institute
Mark Arnold
University of Iowa Roger A. Minear
1 University of Illinois
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0
w David Baker at Urbana-Champaign
1.f University of Tennessee
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05 Omkaram Nalamasu
95- Arindam Bose AT&T Bell Laboratories
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1 Pfizer Central Research
k-
b Vincent Pecoraro
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2 Robert F. Brady, Jr. University of Michigan
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0.1 Naval Research Laboratory
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oi: George W. Roberts
acs.org 1995 | d MChaermyE Edi. tC Caosmteplalnioyn NJoohrtnh CRa. rSolhinaap Sletayt e University
012 | http://pubs.on Date: May 9, MNAUanratitvirhoegnuraasrrilt eyBSt c.o iAfeE nW.l clCeiiss aFc ovonausnninadau atgito hMn adison UDCnooaniuvcte ugUrrlsraritbesyna tnAo aTf. - eICScllhhminnaoimotilshop g aiiegsn C orporation
2, 2cati
uly 2Publi GUnuivnedrsai tIy. oGf Keoarngsa s LD.u PSoonmt asundaram
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Madeleine M. Joullie Michael D. Taylor
University of Pennsylvania Parke-Davis Pharmaceutical Research
Lawrence P. Klemann William C. Walker
Nabisco Foods Group DuPont
Douglas R. Lloyd Peter Willett
The University of Texas at Austin University of Sheffield (England)
In Molecular Action of Insecticides on Ion Channels; Clark, J.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1995.
Foreword
THE ACS SYMPOSIUM SERIES was first published in 1974 to
provide a mechanism for publishing symposia quickly in book
form. The purpose of this series is to publish comprehensive
books developed from symposia, which are usually "snapshots
in time" of the current research being done on a topic, plus
1 some review material on the topic. For this reason, it is neces­
0
0
w sary that the papers be published as quickly as possible.
91.f Before a symposium-based book is put under contract, the
5
5-0 proposed table of contents is reviewed for appropriateness to
9
9 the topic and for comprehensiveness of the collection. Some
1
k- papers are excluded at this point, and others are added to
b
21/ round out the scope of the volume. In addition, a draft of each
0
0.1 paper is peer-reviewed prior to final acceptance or rejection.
1
oi: This anonymous review process is supervised by the organiz­
org 5 | d er^) of the symposium, who become the editor(s) of the book.
cs.99 The authors then revise their papers according to the recom­
a1
bs.9, mendations of both the reviewers and the editors, prepare
012 | http://puon Date: May wvcaihemwoe crAphasa -erpceaeka r drstuh yaal ecrt, oe a poliynln ,lnc ylea ucnodedrsesi dgsau irinbynam lrt ihertvee it ssheviaoeo nrlucfsihm nh aeapls va.pe p aebVpreeese rrnbas namttdoiam dot hreri.ee g pienrdoaidlt ourrecs­­,
2, 2cati tions of previously published papers are not accepted.
uly 2Publi
J
M. Joan Comstock
Series Editor
In Molecular Action of Insecticides on Ion Channels; Clark, J.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1995.
Preface
INSECTICIDES HAVE BEEN THE BOON and the bane of human societies.
Their use has resulted in the most plentiful, least expensive, and most
secure food source thus far produced by our agrarian efforts. As with all
simplistic, directed approaches, the use of insecticides has had far-
reaching and, in most cases, unforeseen environmental impacts.
Nevertheless, it is unlikely that in the near future the quality or quantity
1
00 of foodstuff can be maintained in the absence of pesticidal chemicals, par­
pr
1. ticularly insecticides. Thus, our efforts as pesticide scientists should be
9
05 focused on research approaches that will result in the availability of novel
5-
9 pesticide products that have been evaluated in terms of what we have
9
1
k- learned from past faults in pesticide design and unmanaged overuse.
b
1/ Molecular biological approaches have provided the means to funda­
2
10 mentally change the way in which pesticidal chemicals are discovered and
0.
1 used. Technical knowledge for the production of genetically engineered
org 5 | doi: csoroopn pwlailnl tsb eacnodm be ioetceocnhonmoliocgailclya l fepaessitb lceo. ntBroecl asutrsaet etghiee s laarlrgeea dmy aejxoirsitt ya nodf
acs.199 currently used insecticides are neurotoxic and many are directed toxico-
ubs.y 9, logically to ion-channel disruption, an extensive database is currently
pa
12 | http://n Date: M macivdoaedislea lbssu letco hf o aars ssa esDssseD stshTme a enanddtv .t ahnTeth acugyes,cs ltoahdnei demn deoisss atm devanaydn utbaregi neisgn copofr nnotevrwiidb iumntgioo lwnece oullfl- asintru stdeecicethid­­
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2, 2cati nologies. It is an appropriate time to assess the impact that these molec­
July 2 Publi umlaorle cauplparro paecshteicsi dhea vsec iehnacde .o n pest control and to evaluate the future of

This scenario provided the idealistic focus for the organization of an
ACS symposium entitled "Molecular Action and Pharmacology of Insecti­
cides on Ion Channels", upon which this book is based. Topics were
chosen principally in terms of their contemporary relevance to insect pest
control and concentrated on those aspects in which a molecular under­
standing of insecticide action was being actively researched. Chapters
were then requested from researchers and scholars drawn equally from
academia and industry. These researchers are leading experts in their
chosen areas of study and present a truly international group from
Canada, Israel, Japan, the United Kingdom, and the United States.
This book is divided into three sections, each concerned with the
action of insecticides on a major ion-channel family: voltage-sensitive
channels, ligand-gated channels, and biopesticide-induced channels.
ix
In Molecular Action of Insecticides on Ion Channels; Clark, J.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1995.
Presented in this volume are recent advances in how we envision molecu­
lar binding sites of insecticides on ion channels and molecular alterations
of these sites that result in site-insensitive resistance mechanisms. Addi­
tionally, new receptor-ion channels and mosaic receptor organizations
are described as novel sites of insecticide action and perhaps as means of
genetically managing the development of insecticide resistances in the
future.
I thank the authors for their presentations in the symposium and for
their contributed chapters that encompass this volume. In particular, I
extend my deepest appreciation to the many expert colleagues who pro­
vided helpful and necessary critical reviews. I thank Anne Wilson of ACS
Books for all her help, suggestions, and encouragement; and Margaret
Malone, Amity Lee-Bradley, and Julia Connelly of the Department of
1
0 Entomology, University of Massachusetts, for endless organizational and
0
1.pr editorial concerns. Their efforts and the generous financial support of
9
5 the Division of Agrochemicals of the American Chemical Society; FMC
0
95- Corporation; Ciba-Geigy Corporation; Miles, Inc.; Mycogen Corporation;
9
k-1 NOR-AM Chemical Corporation; Nissan Chemicals of America Corpora­
1/b tion; and Rollins, Inc., made this book possible.
2
0
1
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1 J. MARSHALL CLARK
oi: Department of Entomology
org 5 | d University of Massachusetts
acs.199 Amherst, MA 01003
ubs.y 9,
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uly 2Publi
J

x
In Molecular Action of Insecticides on Ion Channels; Clark, J.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1995.
Chapter 1
Ion-Channel Diversity
Present and Future Roles in Insecticide Action
J. Marshall Clark
1 Department of Entomology, University of Massachusetts,
0
0
h Amherst, MA 01003
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1.
9
5
0
5-
9
9 Insecticides have played an enormous role in the development of
1
k- pesticide and environmental sciences. In our attempts to understand
b
21/ the toxic action of insecticides on target organisms, we have
0
0.1 elucidated many fundamental physiological processes and recently
1
oi: have began the study of these interactions at the molecular level.
cs.org 995 | d pGriovbeanb tlyh en eafifveec tnivoetn teoss h aavned ewnivdies-isopnreeda dth ues een ovfi rionnsmecetnictiadl ecso, nitc ewrnass
ubs.ay 9, 1 tnheagta titvhee auspseec tos fo ft hinesseec ticchiedmesi caanlds thheaisr ucsaeu hseadv.e rNeseuvletretdh einle as sm, uthche
pa
12 | http://n Date: M mtfoatoxeri ceo acdnoymdn apdmleeitgcers aa donafd te ironinvg,io rrooanunmsd eu nnptdraoel brcsloteanmntadsm inaigns asoonfct stih,a etteh dteo ixrw iecinotvhki irnoeenxtimtcesne nsaitnvadel
0o
2, 2cati overuse, such as resistance.
July 2 Publi many inBteercaacuts ed itrheec tllayr gwei tmh aijoonri tcyh aonfn ienlsse cinti cnieduerso anrse annedu reoltsoexwich earned,
an extensive research data base now exists that is available for
assessment. Thus, the most enduring contribution of insecticides
such as DDT, the cyclodienes, etc., may be in providing well-studied
models to assess the advantages or disadvantages of new molecular
biotechnologies as they become available for use in pesticide
science. This aspect, of course, was the focus of the ACS
symposium presentations that served as the template for the
following chapters which comprise this volume.
The past fifty years of agricultural productivity have been largely the result of the
widespread availability of synthetic chemicals, such as fertilizers and pesticides.
These compounds have allowed the farmer to protect the high quality
0097-6156/95/0591-0001$12.75/0
© 1995 American Chemical Society
In Molecular Action of Insecticides on Ion Channels; Clark, J.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1995.
2 MOLECULAR ACTION OF INSECTICIDES ON ION CHANNELS
food and fiber produced with synthetic fertilizers that are necessary to feed and
clothe an ever increasing human population. Currently, the world market value for
pesticides is approximately $23 billion with herbicides, insecticides and fungicides
accounting for 47, 28 and 22% of this total cost, respectively. (1). Even with a
projected growth rate of 10% per annum, the market share for biologicals has been
estimated at 2 to 10% of the total pesticide market share by the year 2000 (2).
Thus, synthetic chemical pesticides will remain the primary method of efficacious
pest control into the next century and, at least in some fashion, well into the future.
As impressive as our progress has been in agriculture, we now face
enormous challenges as pesticide scientists. In five years, we will begin the 21st
century with an estimated world-wide population of 6 billion people (3). This
population is likely to double in only a few decades resulting in tremendous
pressure for agriculture to be even more productive. The past excessive and
indiscriminate use of nonselective pesticides has made these challenges even more
1
00 difficult (4). We now are all aware and concerned about the short and long term
h
1.c effects of pesticides in the environment. Societal response to these concerns has
9
5 resulted in increasingly difficult and costly development and registration processes
0
95- for new and novel pesticides. More disconcerting, perhaps, than even the
9
1 environmental impact that certain pesticides have produced, is the ever increasing
k-
1/b incidence of pests that are resistant to pesticides and the loss of these chemicals as
02 effective pest control agents. Thus, at precisely the time we should be developing
1
0. more selective, biodegradable, efficacious, and environmentally-benign chemical
1
oi: pesticides, we are not even keeping pace with those that are being lost through
org 5 | d regulatory bannings or pest resistance problems.
cs.99 From the above scenario, it follows that the pesticide scientists' most
a1
ubs.y 9, serious task at hand is to begin anew the development of innovative and rational
12 | http://pn Date: Ma mppelaescatiencdsi d feoo nrd etchsrieog png , eplnraoecttkiec c,ot ifob nsioe cl(eh3c)et.mi viiTctyah,le ,a sanend d a dovvpaehnra-crumessea .c moluMosgto ircaeav leo mdidipf fhpearreseivnsic oenuses e odfafs u ttlaotsr gbeinet
0o versus nontarget organisms. Additionally, more natural products should serve as
2, 2cati molecular models for the design of new synthetic but biodegradable pesticides.
uly 2Publi Recent advances in molecular biology have provided a fundamentally novel
J manner in which we analyze the genetic, physiological, and developmental
properties of organisms. Molecular approaches have revolutionized the study of
pesticide mode of action, the determination of selective toxicities of target versus
nontarget organisms, and the elucidation of mechanisms of pest resistance (4). The
availability of such molecula. biological tools has greatly increased our basic
understanding of allied sciences including pharmacology, neurobiology, ion
channel and receptor biology, signal transduction, and developmental biology (5).
From these basic studies, we now have a wealth of new information applicable to
many applied aspects of pesticide science. The technical know-how for the
production of genetically-engineered crop plants and bibtechnological pest control
strategies already exists and will soon be economically feasible (4). Obviously, it is
In Molecular Action of Insecticides on Ion Channels; Clark, J.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1995.
1. CLARK Ion-Channel Diversity 3
an appropriate time to assess the impact that these molecular approaches have had
on pest control and to evaluate the future of molecular pesticide science.
Molecular Basis of Toxicity of Insecticides on Ion Channels
Investigation into the toxic action of insecticidal chemicals has provided much of
the leadership on how we conduct, evaluate, and use mode of action studies on
pesticides and on their environmental impact. Over the past 25 years, these studies
have elucidated new and novel sites of action in insects. Knowledge pertaining to
insecticide receptors and xenobiotic metabolism have allowed the more efficient
design of efficacious analogues. These findings, together with pharmacological and
genetic information, have lead to a fundamentally new way in which insecticides
are being used to suppress the selection of resistant insects. Such approaches are
now well known as resistance management strategies.
1
0
h0 The reasons for these early advancements in the insecticide aspects of
c
1. pesticide science are many. Included in these are that insect pests are particularly
9
05 numerous and potentially devastating to many essential crop systems. Therefore,
5-
9 we allotted a large portion of our effort to find ways to control them. Also, insects
9
1
k- are advanced physiologically and present complex developmental systems, such as
b
1/ the nervous and endocrine systems, that are easily targeted for chemical disruption.
2
10 Of particular importance is the role that Drosophila melanogaster has played in
10. cytological, developmental, and molecular genetic studies in insect and pesticide
oi: science (5).
org 5 | d Pesticide chemists were enormously successful in producing a variety of
acs.199 extremely cheap and effective insecticides by applying the wealth of information
ubs.y 9, obtained from relevant animal studies in neurobiology, pharmacology and
pa
12 | http://n Date: M bmdeeov daeuclotliapvtmoe rebsn yto adfl ivsbariuroiplootuignsyg .i othnOe c fih tnahsneensceetsl e' faunrnelyrcv tpiooruonsds .us yctBsst,ee cmtha ueas nhed uo gifen t hmpiasar,jt oitcrhuietlyrae rw , neborywe a fecoxtuiinnsgtds ataos
uly 22, 20Publicatio rmdoeebvtueaslboto ptlomisxeminc,ot lrooegfc ietchpatelo sdre a tbiaoi onb laocshgeay on,n ne etnhl-vedi irsroterncumtcetedun rteian-las ceftcaitvtiecit iyda ernsed.l atiBimoenpcsaahcuitpsse,s , satoonmxd iec roeoksfii nsttheatenisccese ,
J neurotoxic insecticides are no longer widely used due to environmental concerns
(e.g., DDT, cyclodienes, etc.), their most enduring contribution will most likely be
in providing a historical data base to review and to assess the advantages of various
molecular biological tools as they become available for use in pesticide science.
Ion Channels Perturbed by Insecticides
Neuronal ion channels certainly have been the most widely exploited group of ion
channels in terms of providing a site of action for existing insecticidal chemicals,
however, they are far from the only type of ion channel available for such use. As
more ion channel pharmacology and molecular sequence data is analyzed, it has
become more and more evident that many ion channels, regardless of their tissue
location, share many topological and functional similarities. Such similarities, can
In Molecular Action of Insecticides on Ion Channels; Clark, J.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1995.
4 MOLECULAR ACTION OF INSECTICIDES ON ION CHANNELS
even extend to considerable amino acid and nucleic acid homologies (6). Our
understanding of the basic structure and function of ion channels has been
revolutionized certainly by the use of molecular biology. Specifically, molecular
cloning and sequence analysis of complementary DNAs (cDNAs) have provided
primary structures of ion channels which have allowed the first biochemical-based
interpretation of the tertiary structure of the encoded proteins. Cloned DNAs can
be overexpressed in various cells. Function can then be assigned directly to
specific proteins or polypeptides or indirectly by the use of specific antibodies.
Additionally, oligonucleotide-directed mutagenesis can be used to site-specifically
mutate cDNAs which allows us to test biophysical interpretations concerning
channel kinetics, ion-selectivity, ligand binding domains, etc (6).
Thus, our studies on the molecular action of insecticides on ion channels is
a start to our understanding of these processes and not an end. Such investigations
1 will inevitably elucidate the nature of vulnerable sites for pest insect control which
0
h0 will be of value in parallel research for the control of weeds and microbial
c
1. pathogens and vice versa. Molecular knowledge of the target sites of insecticides,
9
05 natural products, and pharmaceuticals, will be used in the design of new pesticides
5-
9 and in the search of new and novel sites of action.
9
1
k-
b
1/ Voltage-Sensitive Sodium Channels, The voltage-sensitive (or voltage-gated)
2
10 sodium channel is a transmembrane protein complex that is essential in the
0.
1 generation of action potentials in excitable cells, in particular those associated with
oi: the all-or-nothing electrical impulse carried by nerve cell axons (7). On receiving a
org 5 | d depolarisation signal, the permeability of the sodium channel rapidly increases for
acs.199 approximately 1 millisecond. The rising phase of the action potential is due to this
ubs.y 9, increased Na+ permeability and the process that causes it is termed activation. The
12 | http://pn Date: Ma pachcetraimnvnaeetailbo inwl itiypll ruospcueobsnss e dqeuaplesonolta lyrdi seadteteirocmnrei.n aesIsfe dietnhp eoa l arlraeissteas tidoarnnad mp eavrtsoiicls ttasfg,a esth heido epnpe eramnnddeea nbrceiletiu tryon fo ft Not haea+
uly 22, 20Publicatio niitn oanrccetotiuvnardntuisoc ntit noagn da s dtaenttoeenr mcooivnneedrs u ctthhtieen grn aetesxt taa tne2d-. 3v omlTtahigleleiss ede cetopwennodd s.ep nrcoTech eosifss eNpsa,r +o cpaeecsrtsmi veaiastib oitnlei rtyma neadds
J inactivation, allow the voltage-sensitive sodium channel to exist in any one of three
distinct functional states; active, inactive, or resting. Although both inactive and
resting channels are nonconducting, they are very different in how they enter the
"active" conducting state upon depolarisation. An inactivated channel is
recalcitrant to depolarisation and must first return to the resting state by
repolarization prior to being activated.
The primary structures of at least five distinct sodium channels have been
reported (8). These are: 1) the sodium channel from the electric organ of the eel
Electrophorus electricus, 2-4) three separate sodium channels from rat brain (Types
I, II & III); and 5) the ul sodium channel from rat skeletal muscle. All sodium
channels possess an a subunit that is approximately 1,800-2,000 amino acids in
length. The eel electroplax sodium channel is comprised only of an a subunit
whereas the rat skeletal channel has both a and p-1 subunits. The rat brain sodium
In Molecular Action of Insecticides on Ion Channels; Clark, J.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1995.