Lipoxygenase activity in rat kidney glomeruli, glomerular epithelial cells, and cortical tubules.

Abstract

We examined the possibility that renal glomerular and cortical tubular tissue has lipoxygenase activity in addition to the well established cyclo-oxygenase pathway of arachidonic acid metabolism.Homogenized rat kidney glomeruli, in the presence of meclofenamate (33 PM) and divalent cation ionophore A23187 (3 PM), metabolized octatritiated arachidonic acid to 12-hydroxyeicosatetraenoic acid and Iesser amounts of 8-and/or 9-hydroxyeicosatetraenoic acid.These products were identified by thin layer chromatography, high performance liquid chromatography, and gas chromatographymass spectroscopy.In order to rule out the synthesis of hydroxylated fatty acids by platelets and leukocytes entrapped in the glomeruli, we studied lipoxygenase products in glomerular epithelial cells after 9 days in cell culture.Homogenized glomerular epithelial cells converted octatritiated arachidonic acid to 12-hydroxyeicosatetraenoic acid solely.The lipoxygenase activity in cortical tubules was substantially less than in glomeruli and only 12-hydroxyeicosatetraenoic acid was synthesized.The production of hydroxyeicosatetraenoic acid by homogenized glomeruli, glomerular epithelial cells, and cortical tubules was inhibited by three lipoxygenase inhibitors, nordihydroguaiaretic acid, 5,-8,11,14-eicosatetrayoic acid, and 1-phenyl-3-pyrazolidone.These data demonstrate that there is lipoxygenase activity in rat kidney glomeruli, glomerular epithelial cells and to a lesser extent cortical tubules, and may imply a role of the lipoxygenase products in the regulation of normal glomerular function and inflammatory disease of the kidney.Lipoxygenase metabolism of arachidonic acid to monohydroxyeicosatetraenoic acids has been demonstrated in a variety of mammalian ceUs and tissues (Goetzl and Sun, 1979; Siege1 et al., 1979; Herman et al., 1979; Hamberg, 1976; Hamberg et al., 1980; Borgeat and Samuelsson, 1979a).HETEs' have been found to mediate various physiological processes such as histamine secretion from rat mast cells (Sullivan and