The production of the arachidonate metabolite HETE in vascular tissue

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, PGF_2α 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 acid^4,5 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.