Effects of Inhibitors and Substitutes for Chloride in Lumen onp-Aminohippurate Transport by Isolated Perfused Rabbit Renal Proximal Tubules
The transport step for p -aminohippurate (PAH) from cell to lumen across the luminal membrane of rabbit proximal tubules has not been adequately defined. To examine this process more closely, we determined the effects of possible transport inhibitors and substitutes for chloride on PAH secretion in...
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Published in | The Journal of pharmacology and experimental therapeutics Vol. 288; no. 3; p. 993 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
American Society for Pharmacology and Experimental Therapeutics
01.03.1999
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Online Access | Get full text |
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Summary: | The transport step for p -aminohippurate (PAH) from cell to lumen across the luminal membrane of rabbit proximal tubules has not been adequately defined.
To examine this process more closely, we determined the effects of possible transport inhibitors and substitutes for chloride
on PAH secretion in isolated perfused S2 segments of rabbit proximal tubules. The addition of 4-acetamido-4â²-isothiocyano-2,2â²
disulfonic stilbene (10 â4 M) to the perfusate irreversibly inhibited PAH secretion, whereas the addition of probenecid (10 â4 M) to the perfusate reversibly inhibited PAH secretion. PAH secretion was unaffected by thiocyanate replacement of chloride
in the luminal perfusate, reversibly inhibited by 15 to 20% by methyl sulfate replacement, and irreversibly inhibited by isethionate
replacement. Because the luminal membrane is at least as permeable to thiocyanate as to chloride, less permeable to methyl
sulfate, and much less permeable to isethionate, these data suggest that the PAH transport step from cells to lumen does not
require chloride in the lumen but does require a highly permeant anion. During inhibition of PAH transport from cells to lumen,
PAH uptake across the basolateral membrane was also reduced, suggesting some type of feedback inhibition. The data are compatible
with PAH transport across the luminal membrane by an anion exchanger, a potential-driven uniporter, both carriers, or a carrier
that can function in both modes. |
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ISSN: | 0022-3565 1521-0103 |