Abstract
Prostaglandin synthesis requires cyclooxygenase-1 (COX1) or -2 (COX2), which mediate the conversion of arachidonate to prostaglandin H2. COX1 is the predominant constitutive isoform, whereas COX2 expression is typically low. In the present studies we cloned rabbit COX2 and determined its distribution in unstimulated tissues. Screening rabbit eye and uterine libraries yielded two cDNAs containing identical inserts with a 1,812-nucleotide open-reading frame. This encoded a 604-amino acid polypeptide, 90% identical to human, rat, and mouse COX2. Expression of the rabbit COX2 in HEK-293 cells enhanced prostanoid synthesis. Constitutive COX2 mRNA expression was highest in kidney and urinary bladder. COX2 expression was primarily in renal outer medullary interstitial cells with cortical expression in macula densa. In cultured medullary interstitial cells, COX2 mRNA predominated, with little COX1 expression. Interstitial cell COX2 mRNA but not COX1 was induced by phorbol ester and epidermal growth factor but suppressed by dexamethasone. Phorbol ester also upregulated immunoreactive COX2. Constitutive COX2 in these tissues has important implications for side effects of COX2-selective inhibitors.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Cell Line
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Cloning, Molecular
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Cyclooxygenase 1
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Cyclooxygenase 2
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DNA Transposable Elements
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Eicosanoids / metabolism
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Eye / enzymology
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Female
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Gene Expression Regulation, Enzymologic*
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Gene Library
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Humans
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Isoenzymes / biosynthesis*
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Isoenzymes / chemistry
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Isoenzymes / metabolism
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Kidney Medulla / cytology
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Kidney Medulla / enzymology*
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Membrane Proteins
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Mice
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Molecular Sequence Data
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Open Reading Frames
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Prostaglandin-Endoperoxide Synthases / biosynthesis*
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Prostaglandin-Endoperoxide Synthases / chemistry
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Prostaglandin-Endoperoxide Synthases / metabolism
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RNA, Messenger / biosynthesis
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Rabbits
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Rats
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / metabolism
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Sequence Alignment
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Sequence Homology, Amino Acid
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Transcription, Genetic*
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Transfection
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Urinary Bladder / enzymology
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Uterus / enzymology
Substances
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DNA Transposable Elements
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Eicosanoids
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Isoenzymes
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Membrane Proteins
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RNA, Messenger
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Recombinant Proteins
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Cyclooxygenase 1
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Cyclooxygenase 2
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PTGS1 protein, human
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases
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Ptgs1 protein, mouse
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Ptgs1 protein, rat