Until effective insect-selective poisons are discovered, a balance must be established between the need to minimize the adverse environmental impact of insecticides and the need to maximize the survival and health of humans. The long term objective of this proposal is to develop selective insecticides which are toxic to harmful insects but are safe for mammals, birds and fish.
The specific aims are to learn more about major neurotransmitter receptors of insects because of their vital regulatory roles for nerve and muscle functions. Discovery of differences between these receptors and their counterparts in vertebrates may be exploited to develop selective insecticides. Three neurotransmitter receptor systems will be investigated: the acetylcholine, glutamate and Gamma-aminobutyric acid receptors of cockroach ganglia and housefly brain and skeletal muscles. The approach used is biochemical and pharmacological. Two major methods are employed to identify the receptors: One is via their binding sites, utilizing binding assays with radiolabeled neurotransmitters or other receptor ligands. The other is via their functions, utilizing measurements of receptor-regulated ion-transport. Interactions of these receptors with insecticides will determine if these vital proteins may be primary or secondary targets for their actions. In addition, interaction of these receptors with neurotoxic agents present in paralytic venoms of wasps and spiders, and with antibiotics produced by entomophagous fungi will be investigated so as to point to novel structures that may be potent insecticides. The emphasis will be on utilization of our biochemical data and others' electrophysiological data to compare neurotransmitter receptors of insects with those of mammals.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
2R01ES002594-12
Application #
3249912
Study Section
Toxicology Study Section (TOX)
Project Start
1981-04-01
Project End
1992-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
12
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Type
Schools of Medicine
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Jett, D A; Fernando, J C; Eldefrawi, M E et al. (1994) Differential regulation of muscarinic receptor subtypes in rat brain regions by repeated injections of parathion. Toxicol Lett 73:33-41
Eldefrawi, M E; Anis, N A; Eldefrawi, A T (1993) Glutamate receptor inhibitors as potential insecticides. Arch Insect Biochem Physiol 22:25-39
Jett, D A; Hill, E F; Fernando, J C et al. (1993) Down-regulation of muscarinic receptors and the m3 subtype in white-footed mice by dietary exposure to parathion. J Toxicol Environ Health 39:395-415
Abdallah, E A; Jett, D A; Eldefrawi, M E et al. (1992) Differential effects of paraoxon on the M3 muscarinic receptor and its effector system in rat submaxillary gland cells. J Biochem Toxicol 7:125-32
Goodnow Jr, R A; Bukownik, R; Nakanishi, K et al. (1991) Synthesis and binding of [125I2]philanthotoxin-343, [125I2]philanthotoxin-343-lysine, and [125I2]philanthotoxin-343-arginine to rat brain membranes. J Med Chem 34:2389-94
Abdallah, E A; Eldefrawi, M E; Eldefrawi, A T (1991) Pharmacologic characterization of muscarinic receptors of insect brains. Arch Insect Biochem Physiol 17:107-18
Rogers, K R; Cao, C J; Valdes, J J et al. (1991) Acetylcholinesterase fiber-optic biosensor for detection of anticholinesterases. Fundam Appl Toxicol 16:810-20
Jones, M G; Anis, N A; Lodge, D (1990) Philanthotoxin blocks quisqualate-, AMPA- and kainate-, but not NMDA-, induced excitation of rat brainstem neurones in vivo. Br J Pharmacol 101:968-70
Silveira, C L; Eldefrawi, A T; Eldefrawi, M E (1990) Putative M2 muscarinic receptors of rat heart have high affinity for organophosphorus anticholinesterases. Toxicol Appl Pharmacol 103:474-81
Sattelle, D B; Buckingham, S D; Wafford, K A et al. (1989) Actions of the insecticide 2(nitromethylene)tetrahydro-1,3-thiazine on insect and vertebrate nicotinic acetylcholine receptors. Proc R Soc Lond B Biol Sci 237:501-14

Showing the most recent 10 out of 26 publications