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Vol. 298, Issue 3, 1120-1127, September 2001
Department of Physiology, Faculty of Science, Mahidol University,
Bangkok, Thailand
An inhibitory effect of steviol, metabolite of the natural sweetener
stevioside, on transepithelial transport of
p-aminohippurate (JPAH) was
observed in isolated S2 segments of rabbit renal proximal tubules using in vitro microperfusion. Addition of steviol (0.01-0.25 mM) to the bathing medium significantly depressed
JPAH (
50-90%). This inhibitory effect
was dose-dependent and was maximum at a concentration of 0.05 mM. To
further examine this effect, a steviol concentration (0.01 mM) that
produced approximately 50% inhibition of
JPAH, was chosen. Addition of 0.01 mM
steviol to the bathing medium significantly depressed
JPAH by about 50 to 60%. Steviol at the
same concentration (0.01 mM), when present in the tubule lumen, had no
significant effect on JPAH. Addition of 0.01 mM steviol to lumen and bath simultaneously, produced a slightly greater inhibitory effect compared with addition to bath alone (60 versus 70%). A higher concentration of steviol, 0.05 mM (which maximally inhibited JPAH when on the
basolateral side), was required on the luminal side than on the
basolateral side before an inhibitory effect was observed. To further
examine the mechanism by which steviol inhibited
JPAH, its effect on
Na+-K+ ATPase activity and ATP content was
determined. Steviol at concentrations of 0.01 and 0.05 mM had no effect
on Na+-K+ ATPase activity or cell ATP content.
Kinetic analyses indicated that steviol can competitively inhibit PAH
transport at the basolateral membrane. The present study clearly showed
that steviol can have a direct inhibitory effect on renal tubular
transport by competitive binding with organic anion transporter.
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