Enzymic Synthesis of Leukotriene B4 in Guinea Pig Brain

Abstract

Leukotriene B₄ [5(S), 12(R)-dihydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid] was obtained from endogenous arachidonic acid when slices of the guinea pig brain cortex were incubated with the calcium ionophore A 23187. Enzymes involved in its synthesis, arachidonate 5-lipoxygenase [arachidonic acid to 5(S)-hydroperoxy-6-trans-8,11,14-cis-eicosatetraenoic acid and subsequently to leukotriene A₄] and leukotriene A₄ hydrolase (leukotriene A₄ to B₄), were present in the cytosol fraction. Arachidonate 5-lipoxygenase was Ca²⁺-dependent, and was stimulated by ATP and the microsomal membrane, as was noted for the enzyme from mast cells. The lipid hydroperoxides stimulated 5-lipoxygenase by four- to sixfold. The leukotriene A₄ hydrolase activity was rich in brain, and the specific activity (0.4 nmol/min/mg of protein) was much the same as that of guinea pig leukocytes. High activities of these enzymes were detected in the olfactory bulb, pituitary gland, hypothalamus, and cerebral cortex. Since leukotriene B₄ is enzymically synthesized in the brain, possible roles related to neuronal functions or dysfunctions deserve to be examined.