Renal tubular conjugation and excretion of phenol and p-nitrophenol in the chicken: differing mechanisms of renal transfer.

Abstract

Renal tubular formation aud excretion of sulfate and glucuronide conjugates of phenol and p -nitrophenol (PNP) were demonstrated by use of the Sperber chicken preparation. When infused at 1 x 10 -3 µmol/min into one saphenous vein, 80% of the phenol and 53% of the PNP which reached the renal tubules were excreted into the urine. All the excreter phenol and PNP was identified as either the sulfate or glucuronide conjugates. No free phenol or PNP were detected in the urine after their infusion into the renal portal circulation. The renal excretion of phenol (pK a 9.89), which is essentially un-ionized at physiologic pH, was insensitive to inhibition by both organic anion and organic cation competitors and therefore does not appear to involve either organic ion transport system. Renal excretion of PNP (pK a 7.15) was insensitive to inhibition by the organic cation competitor quinine and only a portion appeared sensitive to inhibition by organic anion competitors probenecid and p -aminohippuric acid. Comupetition studies revealed that phenol, PNP, catechol and morphine may compete for renal conjugating enzymes. Phenol or PNP can completely block the renal conjugation of morphine but morphine has virtually no effect on the renal conjugation of phenol and blocks only a portion of the renal conjugation of PNP. A hypothesis is proposed which rationalizes the above differences in inhibition by renal organic ion transport competitors as well as the differences in competition for renal conjugation.