ARACHIDONIC-ACID ABOLISHES THE MITOGEN-INDUCED INCREASE IN CYTOSOLIC-FREE CA2+ AND INTRACELLULAR PH(I) IN RAT THYMOCYTES

The effects of arachidonic acid (AA) and the lectin mitogens, concanavalin A (Con A) and phytohemagglutinin (PHA), on [Ca2+]i and pH(i) in rat thymocytes have been studied by using the intracellular fluorescent probes, Fura-2 and BCECF. It was revealed that exogenous AA (3 muM), in addition to the well-known changes in basal [Ca2+]i and pH(i), also caused a complete blockade of [Ca2+]i and pH(i) signals induced by Con A (10 mug/ml) and PHA (10 mug/ml). In contrast, exposure of thymocytes to mitogens did not prevent the AA-induced increase in [Ca2+]i and decrease in pH(i). In experiments with sodium propionate, the similarity between AA action and EIPA (ethylisopropylamiloride), an inhibitor of Na+/H+ exchangers, was revealed. It is proposed that the inhibitory effect of AA on mitogen-induced lymphocyte proliferation is due primarily to the blockade of transmembrane [Ca2+]i and pH(i) signals, associated with a sustained cytosolic acidification.