title: Identification of an 8-lipoxygenase pathway in nervous tissue of Aplysia californica.
abstract: Arachidonic acid is converted to (8R)-hydroperoxyeicosa-5,9,11, 14-tetraenoic acid (8-HPETE) during incubations with homogenates of the central nervous system of the marine mollusc, Aplysia californica. 8-HPETE can be reduced to the corresponding hydroxy acid or be enzymatically converted to a newly identified metabolite, 8-ketoeicosa-5,9,11,14-tetraenoic acid (8-KETE). These metabolites were identified by high performance liquid chromatography, UV absorbance, and gas chromatography/mass spectrometry. Stereochemical analysis of the products demonstrate that the neuronal enzyme is an (8R)-lipoxygenase. Previously we have shown that the neurotransmitters, histamine and Phe-Met-Arg-Phe-amide, activate 12-lipoxygenase metabolism in isolated identified Aplysia neurons. We now show that acetylcholine activates the (8R)-lipoxygenase pathway within intact nerve cells. Thus, both (12S)- and (8R)-lipoxygenase co-exist in intact Aplysia nervous tissue but are differentially activated by several neurotransmitters. The precise physiological role of the 8-lipoxygenase products is currently under investigation, but by analogy to the well-described 12-lipoxygenase pathway, we suggest that (8R)-HPETE and 8-KETE may serve as second messengers in Aplysia cholinoceptive neurons.
authors.affiliation: Department of Pharmacology, College of Physicians & Surgeons, Columbia University, New York, New York 10032, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Steel
authors.forename: T L
authors.initials: TL
authors.lastname: Tieman
authors.forename: J H
authors.initials: JH
authors.lastname: Schwartz
authors.forename: S J
authors.initials: SJ
authors.lastname: Feinmark
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001048:Aplysia / Q000201:enzymology*; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism; D001091:Arachidonate Lipoxygenases / Q000378:metabolism*; D016718:Arachidonic Acid / Q000378:metabolism; D001095:Arachidonic Acids / Q000378:metabolism; D002490:Central Nervous System / Q000201:enzymology; D002851:Chromatography, High Pressure Liquid; D004789:Enzyme Activation; D008401:Gas Chromatography-Mass Spectrometry; D006632:Histamine / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D066298:In Vitro Techniques; D015289:Leukotrienes / Q000378:metabolism; D009474:Neurons / Q000201:enzymology; D015398:Signal Transduction
chemical_list: C107629:8-keto-5,9,11,14-eicosatetraenoic acid; D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; C047629:8-hydroperoxyeicosatetraenoic acid; D016718:Arachidonic Acid; C047628:8-hydroxyeicosatetraenoic acid; D006632:Histamine; D001091:Arachidonate Lipoxygenases; D001092:Arachidonate 12-Lipoxygenase; C054192:arachidonate 8-lipoxygenase; D000109:Acetylcholine