Renal secretion of phenolsulfonphthalein: analysis of its vectorial transport in normal and mutant analbuminemic rats.
Transtubular transport of many organic anions, such as p-aminohippuric acid and phenolsulfonphthalein (PSP), from plasma into urine is an important renal function. Most of these nephrophilic ligands strongly bind to albumin in the circulation. To investigate a possible function of plasma albumin in vectorial transport of these organic anions, plasma clearance and urinary excretion of PSP, on one hand, and its interaction with serum proteins, on the other, were studied in normal and mutant Nagase analbuminemic rats (NAR). Intravenously administered PSP rapidly disappeared from the circulation, followed by its urinary excretion in both NAR and normal rats. However, its plasma clearance was significantly larger in NAR (53.9 ml/min/kg body weight) than in normal animals (4.7 ml/min/kg body weight). Gel exclusion Sephadex G-100 chromatography and ultrafiltration analysis revealed that the PSP binding capacity of serum proteins was considerably lower in NAR than in normal rats; 32.0% and 12.5% of the ligand bound to NAR serum protein and 94.4% and 84.2% to normal rat serum protein (predominantly albumin) at 0.1 and 0.5 mmol/L ligand concentrations, respectively. Despite the greater PSP clearance in NAR, its urinary excretion was lower in NAR than in the normal animals; 20.9% +/- 2.5% and 46.0% +/- 12.6% of the administered dose appeared in NAR and normal rat urine, respectively, within 3 hours of administration. Injection of PSP with equimolar albumin resulted in a decrease in plasma clearance and an increase in urinary excretion of PSP in NAR; more than 31.4% +/- 3.3% of the injected dose appeared in the urine within 3 hours of administration.(ABSTRACT TRUNCATED AT 250 WORDS)
D000418:Albumins / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002850:Chromatography, Gel; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010635:Phenolphthaleins / Q000378:metabolism*; D010637:Phenolsulfonphthalein / Q000097:blood / Q000378:metabolism* / Q000652:urine; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D013053:Spectrophotometry
D000418:Albumins; D001798:Blood Proteins; D010635:Phenolphthaleins; D010637:Phenolsulfonphthalein