HOE-694 BLOCKS NA+ H+ EXCHANGE IN HUMAN B-LYMPHOBLASTS WITHOUT INFLUENCING PROLIFERATION/

The effect of HOE 694 (3-methylsulfonyl-4-piperidinobenzoyl guanidine hydrochloride), a novel inhibitor of Na+/H+ exchange, on pH(i) recover y from acidification and on proliferation of human B lymphoblasts was investigated. HOE 694 inhibited the Na+/H+ exchanger in a concentratio n-dependent manner. Inhibition constants (K-i) were calculated at 89 /- 5 and 54 +/- 7 nmol/l (means +/- SD; n = 5) at 135 and 79 mmol/l ex ternal Na+, respectively. This indicates a competition of HOE 694 with external Na+ ions at a common binding site of the Na+/H+ exchanger. S ubsequently, the effects of HOE 694 upon DNA synthesis and proliferati on of lymphoblasts were examined. HOE 694 inhibited cell proliferation and DNA synthesis only at concentrations of > 10 mu mol/l. This sugge sts that in the presence of bicarbonate a functionally active Na+/H+ e xchanger is not required for the proliferation of B lymphoblasts.