A functional link between heme oxygenase and cyclo-oxygenase activities in cortical rat astrocytes.
Recent evidence shows that the activation of heme oxygenase (HO) within the CNS is associated with increased prostanoid production. In this study, we investigated whether changes in HO activity induced by pharmacological manipulation are associated with parallel variations in cyclo-oxygenase (COX) activity and prostaglandin production in an in vitro paradigm of CNS cells, i.e. primary cultures of rat cortical astrocytes. Pharmacological tools commonly used to induce changes in HO activity, namely the HO enhancers hemin and CoCl(2) as well as the HO inhibitor Sn-mesoporphyrin-9 (SnMP9), were tested in our model, and the variations in COX activity associated with the above treatments were monitored by measuring a COX end product, prostaglandin E2 (PGE2), released into the incubation medium. We found that the increase in HO activity induced by hemin and/or CoCl(2) was not consistently associated with increases in prostaglandin production, whereas HO inhibition by SnMP9 was normally followed by a decrease in PGE2 release. The above effect was observed after both acute (30 min) and prolonged (24 hr) incubations, suggesting that baseline HO activity contributes to the maintenance of normal PG production in this model. Experiments with the stable HO end products biliverdin and bilirubin suggest that these products may play a role in mediating HO-induced COX activation.
Institute of Pharmacology, Catholic University of Rome, Medical School, Largo Francesco Vito 1, I-00168, Rome, Italy.
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M
Vairano
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Dello Russo
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Pozzoli
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Tringali
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Preziosi
P
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Navarra
D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000201:enzymology*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D020536:Enzyme Activators / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D006427:Hemin / Q000494:pharmacology; D008652:Mesoporphyrins / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism* / Q000502:physiology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D020536:Enzyme Activators; D008652:Mesoporphyrins; D011500:Protein Synthesis Inhibitors; C031468:mesoporphyrin IX; D006427:Hemin; D003513:Cycloheximide; D006419:Heme Oxygenase (Decyclizing); D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone