Identification of an 8-Lipoxygenase Pathway in Nervous Tissue of Aplysia californica

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...

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Bibliographic Details
Published in:The Journal of biological chemistry 1997-07, Vol.272 (30), p.18673-18681
Main Authors: Steel, Douglas J., Tieman, Tamara L., Schwartz, James H., Feinmark, Steven J.
Format: Article
Language:English
Subjects:
Acetylcholine - pharmacology
Animals
Aplysia - enzymology
Aplysia californica
Arachidonate 12-Lipoxygenase - metabolism
Arachidonate Lipoxygenases - metabolism
Arachidonic Acid - metabolism
Arachidonic Acids - metabolism
Central Nervous System - enzymology
Chromatography, High Pressure Liquid
Enzyme Activation
Gas Chromatography-Mass Spectrometry
Histamine - pharmacology
Hydroxyeicosatetraenoic Acids - metabolism
In Vitro Techniques
Leukotrienes - metabolism
Marine
Neurons - enzymology
Signal Transduction
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.272.30.18673