The production of the arachidonate metabolite HETE in vascular tissue

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Abstract

Blood platelets contain two enzyme systems which oxygenate arachidonic acid (AA). First, a cyclooxygenase1 which metabolises AA into the biologically active prostaglandin endoperoxides (PGG2 and PGH2) which are precursors for the platelet prostaglandins PGE2, PGF2α and thromboxane A2 (TxA2). And second, a lipoxygenase that metabolises AA into 12-L-hydroperoxy-5, 8, 10, 14-eicosatetraenoic acid (HPETE)1,2. HPETE is a labile intermediate which is nonenzymatically reduced in aqueous environments to a more stable metabolite, 12-L-hydroxy-5, 8, 10, 14-eicosatetraenoic acid (HETE). HPETE is produced in significant quantities by aggregated platelets, but its exact biological role is not known. Turner et al.3 has suggested that HETE may be a mediator of neutrophil chemotaxis. Vane and coworkers demonstrated that 15-hydroperoxy-5, 8, 10, 14-eicosatetraenoic acid4,5 as well as HPETE were potent inhibitors of prostacyclin (PGI2), the major arachidonate metabolite in vascular tissue. These data suggest that HPETE, if present in vascular tissue, might act as endogenous regulator of PGI2 production. Using radiochemical techniques and mass sspectrometry we have now identified a lipoxygenase enzyme in vascular tissue (rabbit aorta) in which biosynthesis of HETE also occurred. The detection of HETE in this suggests a potential role of the lipoxygenated product as an endogenous regulator of PGI2 biosynthesis.

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Greenwald, J., Bianchine, J. & Wong, L. The production of the arachidonate metabolite HETE in vascular tissue. Nature 281, 588–589 (1979) doi:10.1038/281588a0

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