Organic anion transport by basal-lateral membranes: effect of PAH and furosemide on each other's transport.
The transport of organic anions by the kidney has been shown to be a carrier-mediated process. In an effort to learn more about this process, and examine the potential for two organic anions to compete for the same carrier site, studies were done which involved the transport of p-aminohippuric acid (PAH) and furosemide by vesicles made from basal-lateral membranes of rabbit kidney proximal tubules. Basal-lateral membranes were prepared by differential and ultracentrifugation. The transport was measured by using radiolabelled (3H) organic anions. The transport of each molecule was inhibited by probenecid, indicating that the carrier-mediated process for organic anion transport was functional in these studies. The results indicate that transport of PAH can be inhibited by furosemide in a concentration-dependent manner. This may indicate competition for the same carrier site. Inhibition of furosemide transport by PAH was not significant, perhaps due to much variability in the data. This variability may be due to nonspecific binding of furosemide to the vesicle, higher affinity of furosemide than of PAH for the receptor, or to the presence of more transport carriers for furosemide than for PAH. Experiments were done to determine the extent of nonspecific binding of furosemide. The results show that nonspecific binding of furosemide is extensive, indicating that this may contribute to the differences seen in the inhibition of transport. The data suggest that PAH and furosemide are transported by a common carrier-mediated process in the proximal tubule of the rabbit kidney.
Gloff
C A
CA
Department of Pharmacy, School of Pharmacy, University of California at San Francisco.
Mamelok
R D
RD
Benet
L Z
LZ
D000618:Aminohippuric Acids / Q000493:pharmacokinetics*; D000818:Animals; D001667:Binding, Competitive; D001693:Biological Transport, Active / Q000187:drug effects; D005665:Furosemide / Q000493:pharmacokinetics* / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008566:Membranes / Q000378:metabolism; D011339:Probenecid / Q000494:pharmacology; D011817:Rabbits; D013444:Sulfisoxazole / Q000494:pharmacology; D010130:p-Aminohippuric Acid / Q000493:pharmacokinetics* / Q000494:pharmacology
D000618:Aminohippuric Acids; D013444:Sulfisoxazole; D005665:Furosemide; D011339:Probenecid; D010130:p-Aminohippuric Acid