title: Role of CYP eicosanoids in the regulation of pharyngeal pumping and food uptake in Caenorhabditis elegans.
abstract: Cytochrome P450 (CYP)-dependent eicosanoids comprise epoxy- and hydroxy-metabolites of long-chain PUFAs (LC-PUFAs). In mammals, CYP eicosanoids contribute to the regulation of cardiovascular and renal function. Caenorhabditis elegans produces a large set of CYP eicosanoids; however, their role in worm's physiology is widely unknown. Mutant strains deficient in LC-PUFA/eicosanoid biosynthesis displayed reduced pharyngeal pumping frequencies. This impairment was rescued by long-term eicosapentaenoic and/or arachidonic acid supplementation, but not with a nonmetabolizable LC-PUFA analog. Short-term treatment with 17,18-epoxyeicosatetraenoic acid (17,18-EEQ), the most abundant CYP eicosanoid in C. elegans, was as effective as long-term LC-PUFA supplementation in the mutant strains. In contrast, 20-HETE caused decreased pumping frequencies. The opposite effects of 17,18-EEQ and 20-HETE were mirrored by the actions of neurohormones. 17,18-EEQ mimicked the stimulating effect of serotonin when added to starved worms, whereas 20-HETE shared the inhibitory effect of octopamine in the presence of abundant food. In wild-type worms, serotonin increased free 17,18-EEQ levels, whereas octopamine selectively induced the synthesis of hydroxy-metabolites. These results suggest that CYP eicosanoids may serve as second messengers in the regulation of pharyngeal pumping and food uptake in C. elegans.
authors.affiliation: Department of Biology, Ecology, Humboldt University of Berlin, 10115 Berlin, Germany.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry, University of Texas Southwestern, Dallas, TX 75390.
authors.forename: John R
authors.initials: JR
authors.lastname: Falck
authors.affiliation: Lipidomix GmbH, 13125 Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Rothe
authors.affiliation: Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany.
authors.forename: Wolf-Hagen
authors.initials: WH
authors.lastname: Schunck
authors.affiliation: Department of Biology, Ecology, Humboldt University of Berlin, 10115 Berlin, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Menzel
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004435:Eating; D015777:Eicosanoids / Q000502:physiology*; D005769:Gastrointestinal Motility; D010614:Pharynx / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; D015777:Eicosanoids; D003577:Cytochrome P-450 Enzyme System
keywords: 17,18-epoxyeicosatetraenoic acid; cytochrome P450; fatty acid; lipidomics; omega-3 fatty acids; pharynx