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

Objective The effects of short-term administration of dexamethasone on sodi um/proton antiporter (Na+/H+ antiporter) in human lymphocytes were investig ated in vitro. Methods Cytosolic pH(i) in lymphocytes was measured spectrophotometrically using the pH-sensitive fluorescent dye 2'-7'-bis-carboxyethyl-5(6)-carboxyf luorescein at 530 nm with excitation wavelengths of 440 and 530 nm. The Na/H+ antiporter activity was determined after intracellular acidification us ing 100 mmol/l propionic acid. Results The addition of 1 mu mol/l dexamethasone significantly reduced cyto solic pi-ii from 7.44 +/- 0.03 to 7.25 +/- 0.05 (mean +/- SEM; P< 0.01), In cubation with dexamethasone for 40 min significantly reduced the Na+/H+ ant iporter 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+ antipo rter was not significantly different in the absence or presence of dexameth asone. The inhibition of the Na+/H+ antiporter by dexamethasone was abolish ed in the presence of the glucocorticoid receptor blocker, mifepristone. Conclusion Dexamethasone directly inhibits the Na+/H+ antiporter using a re ceptor-dependent pathway. This effect may be important for pharmacological side effects such as glucocorticoid-induced hypertension. (C) Lippincott Wi lliams & Wilkins.