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Cyclooxygenase Metabolites in the Kidney

  1. Raymond C. Harris,
  2. Ming-Zhi Zhang

Published Online: 1 OCT 2011

DOI: 10.1002/cphy.c100077

Comprehensive Physiology

Comprehensive Physiology

How to Cite

Harris, R. C. and Zhang, M.-Z. 2011. Cyclooxygenase Metabolites in the Kidney. Comprehensive Physiology. 1:1729–1758.

Author Information

  1. George M. O'Brien Kidney and Urologic Diseases Center and Division of Nephrology, Vanderbilt University School of Medicine and Nashville Veterans Affairs Hospital, Nashville, Tennessee

Publication History

  1. Published Online: 1 OCT 2011

Abstract

In the mammalian kidney, prostaglandins (PGs) are important mediators of physiologic processes, including modulation of vascular tone and salt and water. PGs arise from enzymatic metabolism of free arachidonic acid (AA), which is cleaved from membrane phospholipids by phospholipase A2 activity. The cyclooxygenase (COX) enzyme system is a major pathway for metabolism of AA in the kidney. COX are the enzymes responsible for the initial conversion of AA to PGG2 and subsequently to PGH2, which serves as the precursor for subsequent metabolism by PG and thromboxane synthases. In addition to high levels of expression of the “constitutive” rate-limiting enzyme responsible for prostanoid production, COX-1, the “inducible” isoform of cyclooxygenase, COX-2, is also constitutively expressed in the kidney and is highly regulated in response to alterations in intravascular volume. PGs and thromboxane A2 exert their biological functions predominantly through activation of specific 7-transmembrane G-protein-coupled receptors. COX metabolites have been shown to exert important physiologic functions in maintenance of renal blood flow, mediation of renin release and regulation of sodium excretion. In addition to physiologic regulation of prostanoid production in the kidney, increases in prostanoid production are also seen in a variety of inflammatory renal injuries, and COX metabolites may serve as mediators of inflammatory injury in renal disease. © 2011 American Physiological Society. Compr Physiol 1:1729-1758, 2011.