View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Digital Repository @ Iowa State University Iowa State University Capstones, Theses and Graduate Theses and Dissertations Dissertations 2010 Investigation of mechanisms of action of monoterpenoid insecticides on insect gamma- aminobutyric acid receptors and nicotinic acetylcholine receptors Fan Tong Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/etd Part of the Entomology Commons Recommended Citation Tong, Fan, "Investigation of mechanisms of action of monoterpenoid insecticides on insect gamma-aminobutyric acid receptors and nicotinic acetylcholine receptors" (2010). Graduate Theses and Dissertations. 11665. https://lib.dr.iastate.edu/etd/11665 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Graduate Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Investigation of mechanisms of action of monoterpenoid insecticides on insect gamma-aminobutyric acid receptors and nicotinic acetylcholine receptors by Fan Tong A dissertation submitted to the graduate faculty in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Major: Toxicology Program of Study Committee: Joel Coats, Major Professor Timothy Day Richard Martin Russell Jurenka Gary Osweiler Iowa State University Ames, Iowa 2010 Copyright © Fan Tong, 2010. All rights reserved ii TABLE OF CONTENTS CHAPTER 1. GENERAL INTRODUCTION .......................................................... 1 LITERATURE REVIEW ..................................................................................... 1 DISSERTATION ORGNIZATION ..................................................................... 10 TABLES ........................................................................................................... 12 REFERENCES ................................................................................................ 14 CHAPTER 2. EFFECTS OF SOME MONOTERPENOID INSECTICIDES ON [3H]-TBOB BINDING IN HOUSE FLY GABA RECEPTOR AND 36 CL - UPTAKE IN AMERICAN COCKROACH VENTRAL NERVE CORD ..................................... 24 ABSTRACT ..................................................................................................... 24 INTRODUCTION ............................................................................................. 25 MARERIALS AND METHODS ........................................................................ 27 RESULTS ........................................................................................................ 30 DISCUSSION .................................................................................................. 34 REFERENCES ................................................................................................ 40 TABLES ........................................................................................................... 46 FIGURES ........................................................................................................ 47 CHAPTER 3. QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP EVALUATION OF MONOTERPENOID BINDING ACTIVITIES TO HOUSE FLY GABA RECEPTOR ............................................................................................. 58 ABSTRACT ..................................................................................................... 58 INTRODUCTION ............................................................................................. 59 MATERIALS AND METHODS ......................................................................... 61 RESULTS ........................................................................................................ 64 DISCUSSION .................................................................................................. 67 REFERENCES ................................................................................................ 71 iii TABLES ........................................................................................................... 77 FIGURES ........................................................................................................ 80 CHAPTER 4. EFFECTS OF A MONOTERPENOID INSECTICIDE/ACARICIDE, CARVACROL, ON [ 14 C]-NICOTINE BINDING TO THE MUSCA DOMESTICA (HOUSE FLY) NICOTINIC ACETYLCHOLINE RECEPTOR .............................. 85 ABSTRACT ..................................................................................................... 85 INTRODUCTION ............................................................................................. 86 RESULTS ........................................................................................................ 87 DISCUSSION .................................................................................................. 89 MATERIALS AND METHODS ......................................................................... 93 ACKNOWLEDGEMENTS ............................................................................... 95 REFERENCES ................................................................................................ 95 TABLES ........................................................................................................... 99 FIGURES ...................................................................................................... 100 CHAPTER 5. GENERAL CONCLUSIONS ....................................................... 105 ACKNOWLEDGEMENTS ................................................................................ 108 1 CHAPTER 1. GENERAL INTRODUCTION LITERATURE REVIEW Monoterpenoids for pest control Synthetic pesticides play an important role in protecting against pests in agriculture, medicine, industry and the household in the 20th and 21st century. The use of these conventional pesticides is believed to be one of the major reasons for the increase in agricultural productivity in the 20th century. However, there are more and more public concerns all over the world about long-term health and environmental effects concerning the use of synthetic pesticides. Many laboratory studies and clinical cases showed that almost all the conventional synthetic pesticides have the potential to significantly alter ecosystems; and a large number of them have acute or chronic toxicity to humans or other non-target organisms. On the basis of these problems, there is an urgent demand to reduce the use of the conventional pesticides and develop alternatives with fewer harmful effects on the environment and lower toxicity to non-target organisms. For centuries, natural products (such as nicotine from tobacco, pyrethrum from chrysanthemums, rotenone from Derris root, sabadilla from lilies, ryania from the ryania shrub, limonene from citrus peel, and neem from the tropical neem tree) have been used to protect crops from pest invasions in many countries. In recent 2 years, many natural products and their derivatives have been developed and used in commercial pest management to protect crops and human health as alternatives to conventional pesticides. Some of these pesticides have been developed from microbes, such as BT toxins, spinosads, and avermectins [1-3]; some are originally from plants, such as pyrethrins [4], and plant essential oils [5-8]. Among the natural products used for pest control, one of the most successful botanical pesticide groups are monoterpenoids [9], which are mostly found in plant essential oils [5; 10-13]. Monoterpenoids are related to or derived from monoterpenes, a class of terpenes, containing two units of isoprene, and are 10-carbon molecules. These compounds are plant secondary metabolites and play a key role in defending the plants against herbivores or pathogens. For hundreds of years, monoterpenoids have been widely used as food additives, fragrances, decongestants, external analgesics, and antimicrobials [9; 12]. In the past decades, some monoterpenoids have been considered good alternatives for conventional synthetic pesticides for the following reasons. First, these compounds were identified to be good insecticides, acaricides, and insect repellents [5; 7; 8; 10-15]. Many monoterpenoids have shown broad-spectrum insecticidal and acaricidal activities. Table 1 lists some lethal dose 50% (LD 50 ) values of monoterpenoids to different pests. Secondly, monoterpenoids are relatively safe to mammals, aquatic organisms and other non-target organisms [5]. 3 In Table 2, some LD 50 values to mammals are listed. More importantly, most monoterpenoids are biodegradable, and are very friendly to the environment [16-18]. They can be degraded very fast and do not accumulate in the food chain. In Table 3, some environmental fate data of monoterpenoids are shown. In addition, the U.S. Environmental Protection Agency has ruled that many essential oils extracted from plants are exempt from regulation, under special provisions of the Food Quality Protection Act. Possible modes of action of monoterpenoid insecticides Although monoterpenoid pesticides have been developed and studied for many years, their mode of action is not yet very clear. Current evidence indicates that monoterpenoids may act on various targets in insects and mammals, especially on the nervous system, including γ-aminobutyric acid (GABA)-gated chloride