Nicholas R. Ferreri, John C. McGiff, Mairead A. Carroll and John Quilley Pages 613 - 626 ( 14 )
Our initial studies on renal cyclooxygenase (COX)-2 expression and activity addressed the critical role of angiotensin II (Ang II) in increasing tumor necrosis factor alpha (TNF) that eventuated in expression of COX-2 in the medullary thick ascending limb (mTAL) of the nephron. COX-2 supplanted the dominant oxygenase, the cytochrome P450 (CYP) enzyme, w- hydroxylase, that synthesized 20-hydroxyeicosatetraenoic acid (20-HETE). These findings served as the basis for additional studies on: 1) the role of glucocorticoids in regulating COX-2 expression and activity in the mTAL; and 2) the utilization of the same signaling pathways in response to stimulation of the mTAL calcium receptor (CaR). These studies of mTAL COX-2 expression which are addressed in the first part of this chapter are followed by explorations of the expression of COX-2 in preglomerular microvessels (PGMV) and the relationship of COX-2 to 20- HETE, the principal eicosanoid of PGMV. The third and last component of this chapter explores the signaling events, focusing on COX-2, which are set in motion by diabetes.
calcium receptor (car),cyclooxygenase (cox)-2,diabetes,hypertension,prostaglandin e2 (pge2),thick ascending limb (tal),tumor necrosis factor alpha (tnf),20-hydroxyeicosatetraenoic acid (20-hete)
, , , Professor&Chairman, Department of Pharmacology, New York Medical College, Valhalla, New York 10595, USA.