Comparison of cytochrome P450 from an insect and mammal,substrate specificity and the mechanism of selective inhibition
| Project/Area Number |
03660039
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
植物保護
|
|---|
| Research Institution | Chiba University |
|---|
Principal Investigator |
MOTOYAMA Naoki Chiba University, Faculty of Horticulture,Professor, 園芸学部, 教授 (20124662)
|
|---|
| Project Period (FY) |
1991 – 1992
|
| Project Status |
Completed (Fiscal Year 1992)
|
| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1992: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1991: ¥1,600,000 (Direct Cost: ¥1,600,000)
|
|---|
| Keywords | Cytochrome P450 / Methylenedioxyphenyl compounds / Selective inhibition / Insecticidal synergism / Insect / Mammal / Resistance / Monooxygenase system / 殺虫共力剤 |
|---|
| Research Abstract |
A series of methylenedioxyphenyl (MDP) compounds were evaluated for inhibition of degradation of ^<14>C-diazinon by microsomes from the housefly abdomen and rat liver. Several MDP compounds inhibited the insect MFO activity selectively with little effect on the mammalian enzyme system. When these compounds were applied topically to the housefly in combination with diazinon, carbaryl and resmethrin, 3,4-methylenedioxybenzene-1-(2'- methoxyethoxymethyl ether)(referred to as No.1) exhibited an excellent synergism with any of the insecticides tested. The synergism of No.1 was also confirmed against green peach aphids and diamondback moth larvae. The MDP compound showed especially high synergism against pyrethroid resistant strains of insect, restoring the efficacy of insecticide. On the other hand, no synergism was observed when the compound was administered orally to the rat in combination with d-resmethrin.The in vitro and in vivo results suggest the No.1 being a MDP compound with desiable selectivity.
To investigate the mechanism of selectivity, the Type 1 spectra obtained with the rat liver microsomes and several MDP compounds were examined. Since the MDP compounds with selectivity showed significantly smaller Ks values than those without selectivity, a difference in the affinity appears to be involved in the selective inhibition between the insect and mammal. Similarly, the Type 3 spectra obtained with the rat liver microsomes also resulted in smaller peaks at lambda_<427> and lambda_<455> for the selective as compared with non-selective MDP compounds. An attempt to examine the affinity for MDP-cytochrome P450 complex formation using specific cytochrome P450 isozymes responsible for insecticide degradation was not successful due to insufficient amount of the isozymes isolated from the rat liver and housefly abdomen.
|
Report
(3 results)
Research Products
(3 results)
