B. Lal et al., ROLE OF ANION-EXCHANGE AND THIOL-GROUPS IN THE REGULATION OF POTASSIUM EFFLUX BY LEAD IN HUMAN ERYTHROCYTES, Journal of cellular physiology, 167(2), 1996, pp. 222-228
Pb2+ is thought to enter erythrocytes through anion exchange (AE) and
to remain in the cell by binding to thiol groups. To define the role o
f AE mechanism and thiol groups in Pb2+ toxicity, we studied the effec
ts of drugs and conditions that modify AE and that modify thiol groups
on the ability of Pb2+ to stimulate potassium efflux as measured with
Rb-86. The most potent stimulation of Rb-86 efflux by Pb2+ occurred w
hen conditions were optimal for the AE mechanism-that is, when bicarbo
nate was included in the buffer or a buffer made with NaI or NaCl rath
er than NaClO4 or NaNO3 was used. Furthermore, 4,4'-diisothiocyanatost
ilbene-2,2'-disulfonic acid and cetamido-4'-isothiocyanatostilbene-2,2
'-disulfonic acid, potent inhibitors of the AE mechanism, completely i
nhibited stimulation of the Rb-86 efflux by Pb2+. These conditions or
inhibitors did not affect stimulation of the Rb-86 efflux by ionomycin
plus Ca2+. A role for Ca2+ channels was dismissed because the inorgan
ic Ca2+ channel blockers, Cd2+ or Mn2+, did not prevent stimulation of
Rb-86 efflux by Pb2+ but did inhibit stimulation by ionomycin plus Ca
2+. Rb-86 efflux was more sensitive to Pb2+ if erythrocytes were treat
ed for 15 min with thiol-modifying reagents that enter cells, such as
iodoacetamide, N-ethylmaleimide, or dithiothreitol, than to reduced gl
utathione, a thiolmodifying reagent that is not permeable to the cell.
Thus, in erythrocytes the AE mechanism and internal thiol groups are
critical factors that affect the stimulation of a Ca2+-dependent proce
ss by Pb2+. (C) 1996 Wiley-Liss, Inc.