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Functional aspects of eicosanoid metabolism

100%

Carroll M. A., McGiff J. C.

Journal of Physiology and Pharmacology

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1991

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tom 42

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nr 3

The sequential metabolism of eicosanoids by AA oxygenases confers biological properties that may have significant functional implications. Further- the interpretation of the effects of cyclooxygenase inhibitors on eicosanoid, dependent mechanisms needs to be reevaluated. Previously, if cyclooxygenase inhibitors affected the biological action of AA, it was considered to be due to elimination of a prostanoid-mediated component. This interpretation is no longer valid if a cell or tissue has significant P450 and cyclooxygenase activity. The cellular proximity of the P450-dependent monooxygenases and cyclooxygenase, described in tubules, interstitial cells, and blood vessels, may confer a unique ability of A A metabolites to coordinate tubular and vascular function.

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The eicosanoid factor: a determinant of individuality of nephron segments

80%

McGiff J. C., Ferreri N. R., Carroll M. A.

Journal of Physiology and Pharmacology

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2002

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tom 53

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nr 4,1

Nephron function is segmented; each segment has characteristic transport mechanisms and individual eicosanoid profiles. The transport function of the medullary thick ascending limb of Henle's loop (mTAL) establishes the osmolar gradient upon which extra cellular fluid volume (ECFV) conservation depends. The overriding importance of the mTAL to regulation of ECFV is evident in the diuretic- natriuretic potency of furosemide-like agents which target the mTAL. Results: The mTAL has been shown to be heavily invested with cytochrome P450 monooxygenases (CYP), chiefly / -1 hydroxylase activity, that generate 19- and 20-hydroxyeicosatetraenoic acid (HETEs). However, displacement of w hydroxylase by an inducible cyclooxygenase mechanism (COX-2) can be effected by several interventions: long-term infusion of angiotensin II (ANG II), adrenalectomy and elevated extracellular Ca2+ concentrations. This switching mechanism (CYP ³ COX- 2) has been shown to be dependent on activation of tumor necrosis factor alpha (TNFalpha) by ANG II. It represents a long-term adaptive mechanism of the mTAL with production of PGE2 whereas in the short-term, ANG II increases 20-HETE synthesis by the mTAL. The effect of Ca2+ on mTAL eicosanoid-related mechanisms provides an explanation for the natriuretic response to hypercalcemia and diminished ability to concentrate urine. Conclusion: The expression of COX-2 in the TAL has been linked to activation of the renin-angiotensin system, glucocorticoid deficiency and hypercalcemia, all of which operate through a mechanism in which production of TNFa by the TAL is pivotal.

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Regulation of cyclooxygenase isoforms in the renal thick ascending limb: effects of extracellular calcium

80%

Wang D., McGiff J. C., Ferreri N. R.

Journal of Physiology and Pharmacology

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2000

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tom 51

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nr 4,1

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Tubular and vascular actions of cytochrome P450-arachidonate metabolites

80%

Carrol M. A., Balazy M., McGiff J. C.

Journal of Physiology and Pharmacology. Supplement

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1993

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tom 44

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nr 2

Ograniczanie wyników

3 Journal of Physiology and Pharmacology

1 Journal of Physiology and Pharmacology. Supplement

4 McGiff J. C.

2 Carroll M. A.

2 Ferreri N. R.

1 Balazy M.

1 Carrol M. A.

1 Wang D.

1 2002

1 2000

1 1993

1 1991

Functional aspects of eicosanoid metabolism

The eicosanoid factor: a determinant of individuality of nephron segments

Regulation of cyclooxygenase isoforms in the renal thick ascending limb: effects of extracellular calcium

Tubular and vascular actions of cytochrome P450-arachidonate metabolites