title: Juvenile hormone (JH) esterase of the mosquito Culex quinquefasciatus is not a target of the JH analog insecticide methoprene.
abstract: Juvenile hormones (JHs) are essential sesquiterpenes that control insect development and reproduction. JH analog (JHA) insecticides such as methoprene are compounds that mimic the structure and/or biological activity of JH. In this study we obtained a full-length cDNA, cqjhe, from the southern house mosquito Culex quinquefasciatus that encodes CqJHE, an esterase that selectively metabolizes JH. Unlike other recombinant esterases that have been identified from dipteran insects, CqJHE hydrolyzed JH with specificity constant (k(cat)/K(M) ratio) and V(max) values that are common among JH esterases (JHEs). CqJHE showed picomolar sensitivity to OTFP, a JHE-selective inhibitor, but more than 1000-fold lower sensitivity to DFP, a general esterase inhibitor. To our surprise, CqJHE did not metabolize the isopropyl ester of methoprene even when 25 pmol of methoprene was incubated with an amount of CqJHE that was sufficient to hydrolyze 7,200 pmol of JH to JH acid under the same assay conditions. In competition assays in which both JH and methoprene were available to CqJHE, methoprene did not show any inhibitory effects on the JH hydrolysis rate even when methoprene was present in the assay at a 10-fold higher concentration relative to JH. Our findings indicated that JHE is not a molecular target of methoprene. Our findings also do not support the hypothesis that methoprene functions in part by inhibiting the action of JHE.
authors.affiliation: Department of Entomology, University of California Davis, Davis, California, United States of America.
authors.forename: Shizuo G
authors.initials: SG
authors.lastname: Kamita
authors.forename: Aman I
authors.initials: AI
authors.lastname: Samra
authors.forename: Jun-Yan
authors.initials: JY
authors.lastname: Liu
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Cornel
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Hammock
mesh_terms: D000096:Acetone / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism*; D002853:Chromatography, Liquid; D003001:Cloning, Molecular; D003465:Culex / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D018076:DNA, Complementary / Q000235:genetics; D007306:Insecticides / Q000737:chemistry / Q000494:pharmacology*; D007531:Isoflurophate / Q000737:chemistry / Q000494:pharmacology; D007605:Juvenile Hormones / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D013058:Mass Spectrometry; D008726:Methoprene / Q000737:chemistry / Q000494:pharmacology*; D010802:Phylogeny; D011994:Recombinant Proteins / Q000302:isolation & purification
chemical_list: D018076:DNA, Complementary; D007306:Insecticides; D007605:Juvenile Hormones; D011994:Recombinant Proteins; D007531:Isoflurophate; D000096:Acetone; C055697:3-octylthio-1,1,1-trifluoro-2-propanone; D008726:Methoprene; D002265:Carboxylic Ester Hydrolases; C038003:juvenile hormone esterase