Cytochrome P450-derived renal HETEs: storage and release

Kidney International
M A CarrollJ C McGiff

Abstract

We have established an assay based on gas chromatography-mass spectrometry to profile and quantitate endogenous cytochrome P450 monooxygenase (P450)-hydroxyeicosatetraenoic acids (HETEs) exiting the isolated perfused rabbit kidney in response to hormonal stimulation. In response to angiotensin II (Ang II) P450-derived HETEs (16-, 17-, 18-, 19- and 20-) are released from the isolated Kreb's perfused rabbit kidney. Ang II produced a several-fold increase in the levels of P450-HETEs above basal levels in both urinary (such as for 20-HETE from 0.93 +/- 0.7 to 2.31 +/- 0.9 ng/min) and venous (from 0.1 +/- 0.05 to 0.3 +/- 0.05 ng/min) effluents. However, inhibition of P450, which reduced basal release, did not prevent Ang II-induced release of P450-AA products from the rabbit kidney; for example, urinary 20-HETE in the presence of 17-ODYA (1 microM) was undetectable and increased to 0.93 +/- 0.4 ng/min with Ang II and venous 20-HETE increased from 0.06 +/- 0.03 to 0.24 +/- 0.07 ng/min. Similar results were obtained with clotrimazole (1 microM). As 16-, 18-, 19- and 20-HETEs are vasodilators in the rabbit kidney and 16- and 17-HETEs inhibit proximal tubular ATPase activity, we investigated their possible sites of esterification. Corti...Continue Reading

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Citations

Apr 16, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·K Moore
Nov 25, 2003·Prostaglandins & Other Lipid Mediators·David SacerdotiJohn C McGiff
Aug 8, 2002·Kidney International·Hua LiuRadhakrishna Baliga
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