Sulfate homeostasis. IV. Probenecid-induced alterations of inorganic sulfate in rats.
Homeostasis of inorganic sulfate is maintained by the capacity-limited renal reabsorption of sulfate in the proximal tubule. The purpose of the present investigation was to determine if probenecid, the classical inhibitor of renal organic anion secretion, may affect sulfate renal clearance. Two groups of rats were administered in a randomized crossover design, an i.v. bolus dose (20.6 or 92.4 mg/kg) and 4-hr infusion (0.28 or 0.59 mg/min/kg) of probenecid or vehicle, and blood and urine samples were collected. At a steady-state serum concentration of 0.45 mM, probenecid had no significant effect on the serum concentrations or renal clearance of inorganic sulfate, whereas at a serum concentration of 1.4 mM, probenecid treatment caused a significant decrease in serum sulfate concentrations (0.57 +/- 0.11 vs 0.96 +/- 0.19 mM in controls, mean +/- SD, n = 6, P less than 0.001) due to an increase in the renal clearance of sulfate (3.88 +/- 1.18 vs 2.13 +/- 0.84 ml/min/kg in controls, P less than 0.01). The fraction of the filtered sulfate that was reabsorbed was significantly decreased (0.38 +/- 0.23, vs 0.74 +/- 0.09 in controls, P less than 0.01). Therefore, probenecid treatment results in the inhibition of the renal reabsorption of inorganic sulfate in rats in vivo.
Darling
I M
IM
Department of Pharmaceutics, School of Pharmacy, State University of New York, Buffalo, Amherst 14260.
Morris
M E
ME
D000818:Animals; D002118:Calcium / Q000097:blood / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006706:Homeostasis / Q000187:drug effects*; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008274:Magnesium / Q000097:blood / Q000378:metabolism; D010758:Phosphorus / Q000097:blood / Q000378:metabolism; D011188:Potassium / Q000097:blood / Q000378:metabolism; D011339:Probenecid / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D012964:Sodium / Q000097:blood / Q000378:metabolism; D013431:Sulfates / Q000493:pharmacokinetics*
D013431:Sulfates; D010758:Phosphorus; D012964:Sodium; D008274:Magnesium; D011339:Probenecid; D011188:Potassium; D002118:Calcium