PMID- 3182804
OWN - NLM
STAT- MEDLINE
DCOM- 19881214
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 263
IP  - 32
DP  - 1988 Nov 15
TI  - Formation and biological activity of 12-ketoeicosatetraenoic acid in the nervous 
      system of Aplysia.
PG  - 16591-6
AB  - 12-Hydroperoxy-5,8,10,14-eicosatetraenoic acid (12-HPETE), a lipoxygenase 
      product, simulates the synaptic responses 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 (Piomelli, D., 
      Shapiro, E., Feinmark, S. J., and Schwartz, J. H. (1987) J. Neurosci. 7, 
      3675-3886; Shapiro, E., Piomelli, D., Feinmark, S., Vogel, S., Chin, G., and 
      Schwartz, J. H. (1988) Cold Spring Harbor Symp. Quant. Biol. 53, in press). The 
      12-lipoxygenase pathway has not yet been fully characterized, but 12-HPETE is 
      known to be metabolized further. We therefore began to search for other 
      metabolites in order to investigate whether the actions of 12-HPETE might require 
      its conversion to other active products. Here we report the identification of 
      12-keto-5,8,10,14-eicosatetraenoic acid (12-KETE), a metabolite of 12-HPETE 
      formed by Aplysia nervous tissue. This product was identified in incubations of 
      the tissue with arachidonic acid using high performance liquid chromatography, UV 
      spectrometry, and gas chromatography/mass spectrometry. [3H]12-KETE was formed 
      from endogenous lipid stores in nervous tissue, labeled by incubation with 
      [3H]arachidonic acid, when stimulated 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. 
      12(S)-Hydroxy-5,8,10,14-eicosatetraenoic acid, another metabolite of 12-HPETE, is 
      inactive. These results support the hypothesis that 12-HPETE and its metabolite, 
      12-KETE, participate in transduction of histamine responses in Aplysia neurons.
FAU - Piomelli, D
AU  - Piomelli D
AD  - Howard Hughes Medical Institute, Center for Neurobiology and Behavior, Columbia 
      University, New York, New York 10032.
FAU - Feinmark, S J
AU  - Feinmark SJ
FAU - Shapiro, E
AU  - Shapiro E
FAU - Schwartz, J H
AU  - Schwartz JH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (12-keto-5,8,11,13-eicosatetraenoic acid)
RN  - 0 (Arachidonic Acids)
RN  - 0 (Leukotrienes)
RN  - 67675-13-2 (12-HPETE)
RN  - 820484N8I3 (Histamine)
RN  - EC 1.13.11.31 (Arachidonate 12-Lipoxygenase)
SB  - IM
MH  - Animals
MH  - Aplysia/*metabolism
MH  - Arachidonate 12-Lipoxygenase/metabolism
MH  - Arachidonic Acids/*metabolism
MH  - Chromatography, High Pressure Liquid
MH  - Gas Chromatography-Mass Spectrometry
MH  - Histamine/pharmacology
MH  - Leukotrienes/*metabolism
EDAT- 1988/11/15 00:00
MHDA- 1988/11/15 00:01
CRDT- 1988/11/15 00:00
PHST- 1988/11/15 00:00 [pubmed]
PHST- 1988/11/15 00:01 [medline]
PHST- 1988/11/15 00:00 [entrez]
AID - S0021-9258(18)37431-3 [pii]
PST - ppublish
SO  - J Biol Chem. 1988 Nov 15;263(32):16591-6.