THE LIPOXYGENASE INHIBITORS OF ARACHIDONI C-ACID OXIDATION INCREASE CYTOSOLIC-FREE CA2-A( AND H+ IN THYMOCYTES AND BLOCK CHANGES OF THESE PARAMETERS INDUCED BY CONCANAVALIN)

The lipoxygenase inhibitors of arachidonic acid (AA) oxidation, nordih ydroguaiaretic acid (NDGA) and gossypol (Gos), at concentrations of 20 muM and 1.2 muM respectively, have been shown to prevent the Ca2+ sig nal induced by Con A. The lipoxygenase blockers have been demostrated to induce a cytosolic free calcium concentration ([Ca2+]i) rise compar able with that of mitogenic lectins, NDGA or Gos mobilized Ca2+ from i ntracellular stores and enhanced the Ca influx from the extracellular media. The additive effects of NDGA and Gos suggest that there are ind ependent pathways of Ca2+ regulation used-by these agents. NDGA and Go s induced decrease of cytosolic pH (pH(i)) in thymocytes. This effect was not due to the inhibition of Na+/H+-exchanger because it was manif est both in sodium-free media and in the presence of ethylisopropylami loride. NDGA and Gos prevented totally Con A stimulated cytosolic alka lization. The possible mechanisms of action of NDGA and Gos on the maj or parameters of cellular ionic homeostasis - [Ca2+]i and pH(i) - are discussed.