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Abstract

Metabolism of benzidine by a prostaglandin-mediated process in renal inner medullary slices.

N S Rapp, T V Zenser, W W Brown and B B Davis
Journal of Pharmacology and Experimental Therapeutics November 1980, 215 (2) 401-406;
N S Rapp
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T V Zenser
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W W Brown
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B B Davis
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Abstract

Renal inner medullary slices were used to investigate the metabolism and subsequent binding to tissue of [14C]-benzidine metabolite(s) and the effect of benzidine on radioimmunoassayable prostaglandin (PG) E2 synthesis. Benzidine elicited a dose-dependent, reversible inhibition of PGE2 synthesis. By contrast, aspirin inhibition of PGE2 synthesis was not reversible. Binding of [14C]-benzidine metabolite(s) to medullary tissue was observed. This binding was increased by arachidonic acid. Arachidonic acid-mediated binding was prevented by inhibitors of prostaglandin endoperoxide synthetase. Metyrapone and SKF-525A, inhibitors of mixed function oxidase activity, did not inhibit binding of benzidine metabolite(s). Fatty acids which are not substrates for prostaglandin endoperoxide synthetase did not increase binding. These results are consistent with previous studies demonstrating inner medullary microsomal cooxidative metabolism of benzidine by prostaglandin endoperoxide synthetase and document the cooxidative process proceeds in an intact cell preparation, the tissue slice. The renal inner medulla is a potential site for the cooxidative metabolism of drugs and xenobiotics which require activation before eliciting their toxic effects on the urinary tract.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 215, Issue 2
1 Nov 1980
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Abstract

Metabolism of benzidine by a prostaglandin-mediated process in renal inner medullary slices.

N S Rapp, T V Zenser, W W Brown and B B Davis
Journal of Pharmacology and Experimental Therapeutics November 1, 1980, 215 (2) 401-406;

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Abstract

Metabolism of benzidine by a prostaglandin-mediated process in renal inner medullary slices.

N S Rapp, T V Zenser, W W Brown and B B Davis
Journal of Pharmacology and Experimental Therapeutics November 1, 1980, 215 (2) 401-406;
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