HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Haylor, J Articles by Towers, J D Search for Related Content PubMed PubMed Citation Articles by Haylor, J Articles by Towers, J D

Department of Pharmacology, Royal Hallamshire Hospital, Sheffield.

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.

This article has been cited by other articles:

				C. Sauvant, H. Holzinger, and M. Gekle Prostaglandin E2 Inhibits Its Own Renal Transport by Downregulation of Organic Anion Transporters rOAT1 and rOAT3 J. Am. Soc. Nephrol., January 1, 2006; 17(1): 46 - 53. [Abstract] [Full Text] [PDF]