We plan to study toxic effects of chlorinated and pyrethroid pesticides mainly on sodium and calcium regulating processes in the nervous system. To study these pesticide effects on sodium transport specific antibodies directed against sodium channel proteins will be obtained. By using the antibodies, direct interactions of the pesticides with the sodium channels will be studied. The criteria of interactions will be binding, competition against known ligands such as veratridin, phenytoin, RO5-4864, etc., phosphorylation by native and exogenous protein kinases and inhibition of calcium-calmodulin effects. To study the effects of these pesticides on calcium regulatory processes, we plan to use synaptosomal preparations from mammalian brains (mainly rats) and invertebrate central nervous systems (mainly squid). The initial study criterion will be the stimulation of the neurotransmitter release, particularly that caused by Type II pyrethroids. Two major study targets are: Ca-Mg ATPase in the endoplasmic reticulum and calcium-calmodulin-stimulated protein kinase. In the case of the latter, various substrate proteins (e.g., synapsin I, light chain myosin, tubulin, etc.) will be examined to see whether some specific phosphorylation steps are being affected by the changes in the protein kinases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES001963-14
Application #
3249649
Study Section
Toxicology Subcommittee 2 (TOX)
Project Start
1987-12-01
Project End
1992-01-31
Budget Start
1990-02-01
Budget End
1992-01-31
Support Year
14
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of California Davis
Department
Type
Schools of Earth Sciences/Natur
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
Inagaki, S; Kaku, K; Dunlap, D Y et al. (1998) Sequences of cDNAs encoding calmodulin, and partial structures of calmodulin kinase, and a calcium channel of kdr-resistant and -susceptible German cockroaches, Blattella germanica. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 120:225-33
Miyazaki, M; Ohyama, K; Dunlap, D Y et al. (1996) Cloning and sequencing of the para-type sodium channel gene from susceptible and kdr-resistant German cockroaches (Blattella germanica) and house fly (Musca domestica). Mol Gen Genet 252:61-8
Nakagawa, Y; Ishii, S; Matsumura, F (1996) Diflubenzuron stimulates phosphorylation of a 39 kDa integumental protein from newly molted American cockroach (Periplaneta americana). Insect Biochem Mol Biol 26:891-8
Miyazaki, M; Matsumura, F; Beeman, R W (1995) DNA sequence and site of mutation of the GABA receptor of cyclodiene-resistant red flour beetle, Tribolium castaneum. Comp Biochem Physiol B Biochem Mol Biol 111:399-406
Nakagawa, Y; Matsumura, F (1994) Diflubenzuron affects gamma-thioGTP stimulated Ca2+ transport in vitro in intracellular vesicles from the integument of the newly molted American cockroach, Periplaneta americana L. Insect Biochem Mol Biol 24:1009-15
Kaku, K; Matsumura, F (1994) Identification of the site of mutation within the M2 region of the GABA receptor of the cyclodiene-resistant German cockroach. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 108:367-76
Kadous, A; Matsumura, F; Enan, E (1994) High affinity binding of 3H-verapamil to rat brain synaptic membrane is antagonized by pyrethroid insecticides. J Environ Sci Health B 29:855-71
Nakagawa, Y; Matsumura, F; Hashino, Y (1993) Effect of diflubenzuron on incorporation of [3H]-N-acetylglucosamine ([3H]NAGA) into chitin in the intact integument from the newly molted American cockroach Periplaneta americana. Comp Biochem Physiol C 106:711-5
Nakagawa, Y; Matsumura, F (1993) Effect of diflubenzuron on the incorporation of UDP-N-acetyl-[3H]glucosamine (UDP-[3H]NAGA) to chitin in permeabilized, and isolated integuments from the newly molted American cockroach Periplaneta americana. Comp Biochem Physiol C 106:705-10
Enan, E; Matsumura, F (1993) Activation of phosphoinositide/protein kinase C pathway in rat brain tissue by pyrethroids. Biochem Pharmacol 45:703-10

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