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

The lipoxygenase inhibitors of arachidonic acid (AA) oxidation, nordihydroguaiaretic acid (NDGA) and gossypol (Gos), at concentrations of 20 muM and 1.2 muM respectively, have been shown to prevent the Ca2+ signal induced by Con A. The lipoxygenase blockers have been demostrated to induce a cytosolic free calcium concentration ([Ca2+]i) rise comparable with that of mitogenic lectins, NDGA or Gos mobilized Ca2+ from intracellular stores and enhanced the Ca influx from the extracellular media. The additive effects of NDGA and Gos suggest that there are independent pathways of Ca2+ regulation used-by these agents. NDGA and Gos induced decrease of cytosolic pH (pH(i)) in thymocytes. This effect was not due to the inhibition of Na+/H+-exchanger because it was manifest both in sodium-free media and in the presence of ethylisopropylamiloride. NDGA and Gos prevented totally Con A stimulated cytosolic alkalization. The possible mechanisms of action of NDGA and Gos on the major parameters of cellular ionic homeostasis - [Ca2+]i and pH(i) - are discussed.