In this research project we propose to study toxic effects of chlorinated and pyrethroid pesticides mainly on calcium regulating processes in the nervous system, the liver and the heart. The main experimental animals to be used is the rat, but the mouse, the guinea pig, the hamster and some inverterbrate species will also be used. The compounds mainly studied are DDT, toxaphene, chlordane, dieldrin aldrin, neptachlor, neptachlor epoxide, allethrin, permethrin, fenvalerate cypermetnrin and decamethrin. In the case of the liver, the major emphasis will be placed on the long term effects of these chemicals on calcium transport functions of hepatocytes. Also an effort will be made to study their effects on the gap-junction which is known to be controlled by calcium concentration for its functions. The extents of the influence of these pesticides on cell-cell recognition and communication will be determined. In the case of the nervous system, we plan to study their influence on various calcium regulating systems such as Na-Ca exchange, particularly the portion relating to ATP utilization, and on Ca-Mg ATPase. In the latter case changes in its interaction with calmodulin as well as in transmitter release, and neurosecretion will be examined. As for cyclodience-type chlorinated presticides we plan to examine their effects on GABA-chloride channel systems. A particular emphasis will be placed on the studies on the picrotoxinin receptor. This project will also cover the area of pesticide effects on cardiac biochemistry especially as related to their influence on calcium regulation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES001963-09
Application #
3249646
Study Section
Toxicology Study Section (TOX)
Project Start
1977-12-20
Project End
1987-02-14
Budget Start
1986-02-01
Budget End
1987-02-14
Support Year
9
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Michigan State University
Department
Type
Organized Research Units
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
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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