Lithium inhibition of renal tubular p-aminohippurate transport in the rat: relation to plasma 2-oxoglutarate.
Effects of lithium on renal haemodynamics and renal handling of p-aminohippurate (PAH) and 2-oxoglutarate (2-OG) were studied in anaesthetized rats. LiCl given as a single intra-arterial injection of 5 mmol/kg body wt followed by an infusion at 0.01 mmole/min . kg did not affect glomerular filtration rate (Cin) or renal plasma flow (CPAH/EPAH and Cin/Ein). The maximal tubular transport capacity for PAH (TmPAH) was reduced from about 240 to 160 micrograms/min. Simultaneously, lithium significantly raised plasma concentration of 2-OG: its renal clearance increased more than 20 times and net tubular secretion was demonstrated. The inhibition of PAH transport strongly correlated with plasma 2-OG level. The data suggest that lithium inhibits tubular PAH secretion indirectly, by raising plasma 2-OG; the two substances could compete for a common tubular transport mechanism.
D000618:Aminohippuric Acids / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D004305:Dose-Response Relationship, Drug; D007656:Ketoglutaric Acids / Q000097:blood*; D007684:Kidney Tubules / Q000378:metabolism*; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D010949:Plasma / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects; D010130:p-Aminohippuric Acid / Q000378:metabolism*
D000618:Aminohippuric Acids; D007656:Ketoglutaric Acids; D008094:Lithium; D010130:p-Aminohippuric Acid