Effect of dexamethasone on the lymphocytic Na+/H+ antiporter activity

Objective The effects of short-term administration of dexamethasone on sodium/proton antiporter (Na+/H+ antiporter) in human lymphocytes were investigated in vitro. Methods Cytosolic pH(i) in lymphocytes was measured spectrophotometrically using the pH-sensitive fluorescent dye 2'-7'-bis-carboxyethyl-5(6)-carboxyfluorescein at 530 nm with excitation wavelengths of 440 and 530 nm. The Na+/H+ antiporter activity was determined after intracellular acidification using 100 mmol/l propionic acid. Results The addition of 1 mu mol/l dexamethasone significantly reduced cytosolic pi-ii from 7.44 +/- 0.03 to 7.25 +/- 0.05 (mean +/- SEM; P< 0.01), Incubation with dexamethasone for 40 min significantly reduced the Na+/H+ antiporter activity from (9.19 +/- 0.61) x 10(-3) PHi/S (n = 22) to (7.23 +/- 0.49) x 10(-3) pH(i)/s (n = 22; P < 0.01). The effect of dexamethasone was time and concentration dependent The apparent affinity of the Na+/H+ antiporter was not significantly different in the absence or presence of dexamethasone. The inhibition of the Na+/H+ antiporter by dexamethasone was abolished in the presence of the glucocorticoid receptor blocker, mifepristone. Conclusion Dexamethasone directly inhibits the Na+/H+ antiporter using a receptor-dependent pathway. This effect may be important for pharmacological side effects such as glucocorticoid-induced hypertension. (C) Lippincott Williams & Wilkins.