An essential role for vicinal dithiol groups in the catalytic activity of the human placental Na(+)-H+ exchanger.
We examined the effects of phenylarsine oxide, a reagent specific for vicinal dithiol groups, on the catalytic activities, Na+ influx and H+ efflux, of the human placental Na(+)-H+ exchanger. Treatment of the placental brush-border membrane vesicles with the reagent markedly inhibited both the activities. The inhibition was partially reversible by dithiols. The effect of phenylarsine oxide was to reduce the maximal velocity of the exchanger without influencing its affinity for Na+. The exchanger was partially protected from this inhibition by amiloride but not by cimetidine even though both these compounds interacted with the Na(+)-binding site. The data demonstrate that vicinal dithiol groups are essential for the catalytic function of the placental Na(+)-H+ exchanger and that the critical dithiol groups are located at a site distinct from the Na(+)-binding site.
Kulanthaivel
P
P
Department of Cell and Molecular Biology, Medical College of Georgia, Augusta 30912-2100.
Simon
B J
BJ
Leibach
F H
FH
Mahesh
V B
VB
Ganapathy
V
V
D000584:Amiloride / Q000494:pharmacology; D001152:Arsenicals / Q000494:pharmacology*; D001665:Binding Sites; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D002927:Cimetidine / Q000494:pharmacology; D006801:Humans; D006859:Hydrogen / Q000378:metabolism*; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers
D001152:Arsenicals; D002352:Carrier Proteins; D017923:Sodium-Hydrogen Exchangers; C029341:oxophenylarsine; D000584:Amiloride; D006859:Hydrogen; D002927:Cimetidine