title: Induction by alkaloids and phenobarbital of Family 4 Cytochrome P450s in Drosophila: evidence for involvement in host plant utilization.
abstract: In vertebrates, cytochrome P450s of the CYP2 and CYP3 families play a dominant role in drug metabolism, while in insects members of the CYP6 and CYP28 families have been implicated in metabolism of insecticides and toxic natural plant compounds. A degenerate 3' RACE strategy resulted in the identification of fifteen novel P450s from an alkaloid-resistant species of Drosophila. The strong (17.4-fold) and highly specific induction of a single gene (CYP4D10) by the toxic isoquinoline alkaloids of a commonly utilized host-plant (saguaro cactus) provides the first indication that members of the CYP4 family in insects may play an important role in the maintenance of specific insect-host plant relationships. Strong barbiturate inducibility of CYP4D10 and two other D. mettleri P450 sequences of the CYP4 family was also observed, suggesting a pattern of xenobiotic responsiveness more similar to those of several vertebrate drug-metabolizing enzymes than to putative vertebrate CYP4 homologs.
authors.affiliation: Department of Biological Sciences, University of Denver, CO 80208, USA. pdaniels@du.edu
authors.forename: P B
authors.initials: PB
authors.lastname: Danielson
authors.forename: J L
authors.initials: JL
authors.lastname: Foster
authors.forename: M M
authors.initials: MM
authors.lastname: McMahill
authors.forename: M K
authors.initials: MK
authors.lastname: Smith
authors.forename: J C
authors.initials: JC
authors.lastname: Fogleman
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D015152:Blotting, Northern; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D018076:DNA, Complementary / Q000302:isolation & purification; D004330:Drosophila / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D029721:Drosophila Proteins; D004790:Enzyme Induction / Q000187:drug effects / Q000235:genetics; D005260:Female; D008969:Molecular Sequence Data; D010634:Phenobarbital / Q000494:pharmacology*; D010802:Phylogeny; D010944:Plants / Q000201:enzymology / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects; D015262:Xenobiotics / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D018076:DNA, Complementary; D029721:Drosophila Proteins; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; C114507:CYP4D10 protein, Drosophila; D010634:Phenobarbital