AJP - Gastrointestinal and Liver Physiology, Vol 248, Issue 2 238-G245, Copyright © 1985 by American Physiological Society
Sulfobromophthalein inhibition of glutathione and methylmercury secretion into bile
N. Ballatori and T. W. Clarkson
The mechanism through which sulfobromophthalein (BSP) inhibits the biliary
secretion of glutathione (GSH) and methylmercury was examined in male rats
anesthetized with pentobarbital sodium. The biliary secretion rates of GSH
and methylmercury were measured following the bolus intravenous
administration of various doses of BSP, the GSH conjugate of BSP (BSP-SG),
and phenol-3,6-dibromphthalein disulfonate (DBSP, a nonmetabolizable
analogue of BSP). The effects of BSP on GSH secretion were dose dependent;
at a dose of 120 mumol/kg the rate of GSH secretion fell close to zero.
DBSP also inhibited GSH secretion, although the inhibition was not as
complete as observed after BSP administration; at a dose of 180 mumol/kg
GSH secretion fell to 18% of control. BSP-SG, in contrast, had no effect on
GSH secretion into bile when given at a dose of 120 mumol/kg. At doses of
240 and 360 mumol BSP-SG/kg, there were only minor changes in the rate of
GSH secretion. The changes in GSH secretion induced by these dyes were
accompanied by proportional changes in glutathione disulfide (GSSG)
secretion into bile, so that the molar ratio of GSSG to GSH in bile
remained within the range of 0.07-0.18. In all experiments the changes in
methylmercury secretion were parallel to the changes in GSH secretion. The
results suggest that the BSP-induced inhibition of GSH, GSSG, and
methylmercury secretion into bile is due to the direct inhibition of the
biliary GSH transport process.
