Tubular mechanisms determining the urinary excretion of tritiated prostaglandin E2 in the anaesthetized rat.

1. The renal excretion of arterially injected tritiated prostaglandin E2 ([3H]PGE2) and its metabolites has been examined in the anaesthetized rat before and after the administration of probenecid (an inhibitor of proximal organic acid secretion). [14C]Inulin was employed as a freely filtered, non-reabsorbable marker, while [3H]p-aminohippurate was used to assess the inhibitory effect of probenecid. The experiments allowed us to quantify the tubular delivery, proximal secretion, intratubular metabolism, and tubular reabsorption of [3H]PGE2 by the whole kidney in vivo. 2. Following a single pass through the left kidney 25% of an injected dose of [3H]PGE2 was excreted, although only 1.7% of the injected 3H co-chromatogrammed with cold PGE2. The chemical content of PGE2 in the isotope employed, produced a slight but significant (P less than 0.05) fall (12%) in the single-pass excretion of [14C]inulin. 3. Intravenous probenecid (100 mg kg-1 + 100 mg kg-1 h-1) completely inhibited the proximal tubular secretion of [3H]p-aminohippurate, while the single-pass excretion of [14C]inulin remained unchanged. Probenecid also reduced the blood pressure and urine flow, and decreased the binding of [3H]PGE2 to plasma protein from 59 to 41%. 4. Probenecid administration reduced the single-pass excretion of 3H following an injection of [3H]PGE2 by 65% down to 8.5% of the injected dose. Due to the change in protein binding however, probenecid also increased the filtered load of [3H]PGE2 from 12 to 16% of the injected dose. 5. The following calculations were made concerning the tubular handling of [3H]PGE2 by the whole kidney in vivo. (i) Thirty-five per cent of the injected dose of [3H]PGE2 was secreted by the proximal tubules on a single pass through the kidney, in addition 12% was filtered while 59% was protein bound. (ii) The tubular reabsorption of [3H]PGE2 was 47% of the filtered load. (iii) [3H]PGE2 was subject to a high degree of intratubular metabolism which at a minimum value represented about 50% of the filtered load. The metabolism of [3H]PGE2 also occurred during proximal tubular secretion.