Induction of cyclooxygenase-2 in thick ascending limb cells by adrenalectomy.
Adrenalectomized (ADX) and sham-operated rats received either dexamethasone (DEX) or vehicle. Renal tissue was used for morphologic analysis, assessment of cyclooxygenase-2 (COX-2) protein expression and mRNA accumulation, and quantitation of COX-2 activity. In untreated or shamoperated rats, COX-2 protein was observed in a subset of tubular epithelial cells (<2%), which were located mainly in the cortex. All COX-2-positive cells also expressed Tamm-Horsfall glycoprotein, a highly selective marker for thick ascending limb (TAL) cells. After ADX, >30% of TAL cells expressed COX-2 in a manner consistent with recruitment of COX-2-positive TAL cells toward the medulla. Treatment of ADX rats with DEX reduced the number of COX-2-positive cells to that observed in sham-operated or intact rats. COX-2 mRNA accumulation was increased by ADX and partially attenuated by treatment with DEX. Western blot analysis of cortical microsomes revealed a substantial increase in COX-2 expression in ADX rats, compared with ADX/DEX-treated, sham-operated, or intact rats. The increase in COX-2 protein expression was associated with a twofold increase in prostaglandin E(2) formation by cortical microsomes obtained from ADX rats, compared with sham-operated rats. It is concluded that ADX induces expression of enzymatically active COX-2, such that expression occurs in the cortical TAL and proceeds in a defined pattern toward the outer medullary TAL. It is suggested that ADX induces expression of TAL cells that, in the basal state, do not express COX-2 protein.
Vio
Carlos P
CP
Departamento de Ciencias Fisiologicas, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, Chile.
An
Shao-Jian
SJ
Department of Pharmacology, New York Medical College, Valhalla, New York.
Céspedes
Carlos
C
Departamento de Ciencias Fisiologicas, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, Chile.
McGiff
John C
JC
Department of Pharmacology, New York Medical College, Valhalla, New York.
Ferreri
Nicholas R
NR
Department of Pharmacology, New York Medical College, Valhalla, New York.
D000315:Adrenalectomy; D000818:Animals; D051546:Cyclooxygenase 2; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000201:enzymology; D008138:Loop of Henle / Q000166:cytology / Q000201:enzymology*; D008264:Macrophages / Q000201:enzymology; D008297:Male; D011184:Postoperative Period; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D005938:Glucocorticoids; D007527:Isoenzymes; D012333:RNA, Messenger; D003907:Dexamethasone; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases