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 pHi 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 micromol/l dexamethasone significantly reduced cytosolic pHi 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)x10(-3) pHi/s (n = 22) to (7.23+/-0.49)x10(-3) pHi/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.


CONCLUSIONS
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.
Tepel
M
M
Medizinische Klinik I, Universitätsklinik Marienhospital, Ruhr-Universität Bochum, Germany.
Pytlik
M
M
van der Giet
M
M
Schlüter
H
H
Jankowski
J
J
Zidek
W
W
D003600:Cytosol / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D015735:Mifepristone / Q000494:pharmacology; D009994:Osmolar Concentration; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013997:Time Factors
D005938:Glucocorticoids; D006727:Hormone Antagonists; D017923:Sodium-Hydrogen Exchangers; D015735:Mifepristone; D003907:Dexamethasone