12-keto-eicosatetraenoic acid. A biologically active eicosanoid in the nervous system of Aplysia.
The lipoxygenase product 12-hydroperoxy-5,8,10,14-eicosatetraenoic acid (12-HPETE), stimulates the synaptic response produced by the modulatory transmitter histamine and the neuroactive peptide Phe-Met-Arg-Phe-amide (FMRFamide) in identified neurons of the marine mollusk Aplysia californica. The 12-lipoxygenase pathway has not yet been fully characterized, but 12-HPETE is known to be metabolized further. Therefore, we began to search for other metabolites in order to investigate whether the actions of 12-HPETE might require its conversion to other active products. We have identified 12-keto-5,8,10,14-eicosatetraenoic acid (12-KETE) as a metabolite of 12-HPETE formed by Aplysia nervous tissue. 12-KETE was identified in incubations of the tissue with arachidonic acid using HPLC, UV spectrometry, and gas-chromatography/mass spectrometry. [3H]12-KETE is formed from endogenous lipid stores in nervous tissue, labeled with [3H]arachidonic acid upon stimulation by application of histamine. In L14 and L10 cells, identified neurons in the abdominal ganglion, applications of 12-KETE elicit changes in membrane potential similar to those evoked by histamine. Another metabolite of 12-HPETE, 12(s)-hydroxy-5,8,10,14-eicosatetraenoic acid [12(S)-HETE], is inactive. These results support the hypothesis that 12-HPETE and its metabolite, 12-KETE, participate in transduction of histamine responses in Aplysia neurons.
Howard Hughes Medical Institute, Columbia University, New York, New York 10032.
D
D
Piomelli
S J
SJ
Feinmark
E
E
Shapiro
J H
JH
Schwartz
D000818:Animals; D001048:Aplysia; D001095:Arachidonic Acids / Q000096:biosynthesis / Q000302:isolation & purification*; D002851:Chromatography, High Pressure Liquid; D005724:Ganglia / Q000502:physiology*; D008401:Gas Chromatography-Mass Spectrometry; D066298:In Vitro Techniques; D009420:Nervous System / Q000032:analysis* / Q000378:metabolism
C054994:12-keto-5,8,11,13-eicosatetraenoic acid; D001095:Arachidonic Acids