Regulation of renal cortical cyclooxygenase-2 in young rats
Ming-Zhi Zhang, Su-wan Wang, Huifang Cheng, Yahua Zhang, James A. McKanna, Raymond C. Harris
AJP - Renal Physiology
is involved in kidney morphogenesis and is transiently elevated in the immature kidney. In adult rats, renal cortical COX-2 expression is tonically suppressed by mineralocorticoids (MC) and glucocorticoids (GC) and induced by chronic salt restriction. Young rats have low levels of GC and are in a state of relative volume depletion. The present study was designed to investigate the mechanisms underlying elevated cortical COX-2 expression in the immature kidney. Supplementation of GC or MC
... sed cortical COX-2 expression in suckling rats. GC suppression was significantly, but not completely, prevented by either an MC receptor antagonist or a GC receptor antagonist. MC suppression was completely prevented by a mineralocorticoid receptor antagonist. Salt supplementation suppressed cortical COX-2 expression in a dose-and time-dependent pattern in the suckling rats. Cortical COX-2 expression in the weanling rats was upregulated by a low-salt diet and downregulated by a high-salt diet. These results suggest that relative volume depletion and reduced GC levels are involved in elevated cortical COX-2 expression in the immature rodent kidney. prostaglandin synthase G2/H2; mineralocorticoid; glucocorticoid; salt supplementation PROSTAGLANDINS ARE INVOLVED in mammalian kidney development, and they also regulate renal vascular tone and salt and water homeostasis in adult kidneys (11, 12, 18, 22, 27, 37) . Prostaglandin production depends on three key steps: 1) release of arachidonic acid from membrane phospholipids by phospholipase A 2 ; 2) conversion of the arachidonic acid to PGH 2 by cyclooxygenase (COX); and 3) further metabolism by specific prostaglandin synthases. Two separate gene products with COX activity have been described, 20, 29) . The "constitutive" COX-1 gene encodes a 2.7-to 2.9-kb transcript of COX-1, whereas the COX-2 gene encodes a 4.5-kb transcript that is "inducible" and glucocorticoid sensitive. In the kidney, COX-1 has been localized to mesangial cells, arteriolar endothelial cells, parietal epithelial cells of Bowman's capsule, collecting duct epithelial cells (both cortical and medullary), and medullary interstitial cells (33).