Neurotoxicology of Insecticides and Pheromones

303 Pages·1979·9.081 MB·English

by  Toshio Narahashi (auth.), Toshio Narahashi (eds.)

Neurotoxicology 01
Insecticides and
Plieromones
Neurotoxicology oj
Insecticides and
Pneromones
Edited by
ToShio Narahashi
Northwestern Universnv
Chicago, Illinois
PLENUM PRESS • NEW YORK AND LONDON
Library of Congress Cataloging in Publication Data
Symposium on Chemistry of Neurohormones and Neurotransmission, Anaheim, Calif., 1978.
Neurotoxicology of insecticides and pheromones.
"Proceedings of the Symposium on Chemistry of Neurohormones and Neurotransmission held in
conjunction with the 175th anniversary of the American Chemical Society, at Anaheim, California,
March 14-15,1978."
Includes index.
1. Pesticides - Physiological effect - Congresses. 2. Neurotoxic agents - Physiological effect
Congresses. 3. Pheromones - Physiological effect - Congresses. 4. Insects - Physiology - Con
gresses. I. Narahashi, Toshio. II. American Chemical Society. III. Title.
S8951.5.595 1978 595.7'02'4 78-10913
ISBN-13:978-1-4684-0972-7 e-ISBN-13:978-1-4684-0970-3
DOl: 10.1007/978-1-4684-0970-3
Proceedings of the Symposium on Chemistry of Neurohormones and
Neurotransmission held in conjunction with the 175th Anniversary of
the American Chemical Society, at Anaheim, California, March 14-15, 1978
© 1979 Plenum Press, New York
Softcover reprint of the hardcover lst edition 1979
A Division of Plenum Publishing Corporation
227 West 17th Street, New York, N.Y. 10011
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted,
in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording, or otherwise, without written permission from the Publisher
Preface
Substantial progress has been made during the past three
decades in the development of a variety of chemical means to control
insect pests. A large number of highly effective insecticides have
been developed, and many of them have contributed to a great extent
to increasing agricultural productivity and eradicating diseases
transmitted by vectors. However, contamination of our environment
caused by various pesticides has become a serious problem, and
various attempts have been made to develop newer methods of con
trolling insect pests. One of the approaches is to develop newer
insecticides which cause less contamination of the environment
without losing their insecticidal potencies. Another approach,
among other things, is to utilize pheromones to control certain
species of insects.
No matter what approach one may choose, it is imperative to
understand the mechanism of action of pesticides for efficient
development and utilization of these chemicals. One important
feature common to most insecticides and pheromones is their inter
action with the nervous system which is the main target site.
Thus the mechanisms of action of these chemicals on the nervous
system represent one of the most critical aspects in pesticide
toxicology. In comparison to the chemical and biochemical studies
dealing with the metabolism of various pesticides, the study of
neurotoxicology has lagged behind to a considerable extent for
various reasons. Technical complications involved in neurotoxi-
co logical experiments appear to be one of the contributing factors.
Unlike the two-dimensional scheme of the pesticide metabolism study,
neurotoxicological study involved multi-dimensional factors such as
the physico-chemical nature of membrane permeability, enzymatic
reactions, and the integrated nervous function as an organ.
Recognizing the critical importance of neurotoxicology in
further development of effective chemical means of pest control,
the Division of Pesticide Chemistry of the American Chemical Society
held a Symposium on Chemistry of Neurohormones and Neurotransmission
on March 14 and 15, 1978, in conjunction with the 175th National
Meeting of the American Chemical Society at Anaheim, California.
v
PREFACE
The purpose of this Symposium was to provide a forum where a variety
of scientists who were interested in the interactions of insecti
cides and pheromones with the nervous system got together to exchange
their views. Thus chemists, biochemists, electrophysiologists and
neurochemists gathered, and thirteen papers were presented. Three
of them dealt with pheromones and chemical perception, seven
papers were concerned with the electrophysiological modes of action
of insecticides on the nervous system, and three papers were related
to the neurochemical modes of action of insecticides. This book
represents the publication of all these papers. It is my hope that
this publication will be a useful reference in the field of pesti
cide neurotoxicology and that it will provide the basis on which
further advancement in nerurotoxicology is made.
Toshio Narahashi
Contents
Introduction: Nervous System as a Target Site . . . . . . .
of Pheromones and Insecticides • • • 1
Toshio Narahashi
Pheromone Perception in Lepidoptera •••••••• • • • • 5
Wendell L. Roelofs
Pheromone and Host Odor Perception • • • • • • • • • • • •• 27
Thomas L. Payne
Chemoreceptor Proteins 59
Dale M. Norris
Mode of Action of Insecticides: Insights Gained
from Neurophysiological Preparations of
Intact or Dissected Insects •••••• 79
Thomas A. Miller
An Analysis of the Temperature-Dependence of the
Toxicity of Allethrin to the Cockroach 97
Derek W. GaIlDl10n
The Comparative Neurotoxicity of Formamidine
Pesticides • • • • • • • • • • • • 119
Albert E. Lund, Robert M. Hollingworth,
George K.W. Yim
Action of Dieldrin and Related Compounds on
Synaptic Transmission • • • • 139
Daniel L. Shankland
Effects of Parathion on the Mammalian Nervous
System • • • • • • • • • • • • 155
Dorothy E. Woolley, James R. Chernobieff,
Lawrence W. Reiter
vii
viii CONTENTS
Effects of Insecticides on the Sensory
Nervous System • 183
Joep van den Bercken, Alfons B.A, Kroese,
Louis M.A. Akkermans
Nerve Membrane Ionic Channels as the Target
Site of Insecticides • • ••• 211
Toshio Narahashi
Characteristics of DDT-Sensitive Ca-ATPase"
in the Axonic Membrane 245
Fumio Matsumura and S.M. Ghiasuddin
Interaction of Insecticides with Acetylcholine
Receptors • • • • • • • • • • • 259
Stephen W. Jones, Puppala Sudershan,
Richard D. O'Brien
Effect of Structure on the Interaction of
Organophosphorus and Carbamate
Esters with Acetylcholinesterase 277
T. Roy Fukuto
Contributors • • 297
Index 301
INTRODUCTION: NERVOUS SYSTEM AS A TARGET SITE OF PHEROMONES AND
INSECTICIDES
Toshio Narahashi
Department of Pharmacology, Northwestern University
Medical School, Chicago, Illinois 60611
The chemistry of neurohormones and insecticides has achieved
remarkable progress during the past decade or two. These chemicals
act primarily on the nervous system of insects thereby exerting
unique effects. Neurotoxicological studies have also made sub
stantial progress recently. However, there has been virtually no
chance for both chemists and neurotoxicologists to get together to
exchange views. The time is ripe and this symposium is going to
provide them with a unique forum to bring their current data
together.
Behavioral responses induced in insects by pheromones are
undoubtedly the result of stimulation of the sensory nervous sys
tem. Electrophysiological techniques have clearly demonstrated
such responses in the insect antennae. Specificity of the pheromone
induced behavior is due to the specific configuration of the
sensory receptor and its specific affinity for the pheromone, but
the detailed molecular mechanism of such interaction between the
pheromone and the receptor remains largely to be explored.
For most insecticides currently in use, it has clearly been
established that the nervous system is the major target site.
However, the mechanism of action on the nerve is considerably diff
erent among those insecticides acting on the nerve. Cholinesterases
in the nervous system are indeed the prime target for certain in
secticides such as organophosphates and carbamates, whereas no
specific enzyme system has been clearly established as the target
for some other insecticides. It should be emphasized that
excitation of the nerve takes place as a result of changes in nerve
membrane permeabilities to ions such as sodium and potassium.
These permeability changes are physico-chemical phenomena of the
2 TOSHIO NARAHASHI
membrane not dependent upon the metabolic energy, and the sites of
ion permeation are called "ionic channels" which have been shown to
be holes, not carrier mechanisms. It has indeed been demonstrated
that permeabilities of ionic channels are drastically altered by
certain chlorinated hydrocarbon and pyrethroid insecticides thereby
causing severe symptoms of poisoning in the nervous system.
Studies of the insecticidal action on the nervous system are
of importance in various respects. It is quite obvious that the
interactions between insecticides and nerve membranes must be
explored in order to understand the molecular mechanism of action
of insecticides. Besides this, the study of insecticides with the
nervous system has a great impact on our understanding of the
structure-activity relationship of insecticides.
In order to establish the structure-activity relationship for
any group of insecticides acting primarily on the nervous system,
we have to understand the processes of toxic action of insecticides.
There are at least three major steps for an insecticide to exert
its killing action on insects, i.e. penetration through the cuticle
or other routes, activation and/or detoxication, and action on the
target nerve. In addition, a variety of reactions may be inter
posed during these processes. Thus the potency of an insecticide
to kill insects is a final manifestation of a series of complex
reactions, and it could be misleading to relate the molecular
structure of insecticides to the killing potency. The structure
must be compared with the action on the target site. This is
relatively easy if we can isolate the target component in vitro,
and much progress has indeed been made along this line using organo
phosphate and carbamate insecticides which inhibit cholinesterases
(Fukuto, 1971; Metcalf, 1971).
However, experiments are more complicated for many other
insecticides because their effects must be compared on the nerve.
We have recently developed a technique whereby a large number of
insecticide derivatives can be compared for their direct effect on
the isolated crayfish abdominal nerve cord which is fairly sensi
tive to many insecticides (Takeno et al., 1977). Through the
study of a variety of synthetic pyrethroids it has been found that
the potency on the nerve and the potency to kill insects do not
necessarily run parallel with each other. Some pyrethroids are
potent neuropoisons but lack strong insecticidal activity, whereas
some others are relatively weak on the nerve yet can kill insects
effectively. One such example is shown in Table 1. The potency
to stimulate the nerve is measured as the concentration to stimu
late the frequency of spontaneous discharges of the crayfish
abdominal nerve cord to 200% of the control level (nerve stimulation
200 or NS200), and the insecticide potency is measured as LCSO'
Although (-)-trans phenothrin is only about half as potent as
(+)-trans phenothrin in stimulating the nerve, the former virtually
INTRODUCTION: NERVOUS SYSTEM AS TARGET SITE 3
Table 1. Potencies of phenothrin in stimulating
the crayfish abdominal nerve cord and in killing
houseflies.
Compounds NS200 LC50
(xlO-8M) (xlO-4M)
(+)-trans phenothrin 5.2 4.85
(-)-trans phenothrin 11.5 >143
(+)-cis phenothrin 6.8 5.71
(-)-cis phenothrin 102 114
lacks insecticidal potency while the latter is a potent insecticide.
On the other hand, the correlation between the nerve and insectici
dal potencies is good for (+)- and (-)-cis phenothrin. This example
clearly indicates the need for comparing the direct action on the
target site for the purpose of elucidating the true structure
activity relationship. There are a number of such interesting
examples (Narahashi, 1978; Nishimura and Narahashi, 1978; Narahashi
et a1., 1977).
The topics covered by the present symposium may be divided into
three large categories, i.e. pheromone perception and receptors
(W.L. Roelofs, T.L. Payne and D.M. Norris), neurophysiology of
insecticide action (T.A. Miller, D.W. Gammon, A.E. Lund, D.L.
Shankland, D.E. Woolley, J. van den Bercken and T. Narahashi), and
neurochemistry of insecticide action (F. Matsumura, R.D. O'Brien
and T.R. Fukuto). The aim of this symposium is not only to provide
a forum to present current developments in this field but also to
facilitate communications and collaborations between chemists and
neurotoxicologists for further advancement of newer pest control
techniques.
REFERENCES
Fukuto, T.R., 1971, Relationships between the structure of organo
phosphorus compounds and their activity as acetylcholinester
ase inhibitors, Bull. W.H.O. 44: 31-42.
Metcalf, R.L., 1971, Structure-activity relationships for insecti
cidal carbamates, Bull. W.H.O. 44: 43-78.
Narahashi, T., 1978, Neurophysiological study of the structure
activity relations of insecticides, in: Pesticides and Venom
Neurotoxicity, ed. D.L. Shankland, R.M. Hollingworth and T.
Smyth, Jr., Plenum, New York. p. 119-131.