Istituto di Fisiologia Clinica     
Coceani F., Ackerley C., Seidlitz E., Kelsey L. Function of cyclo-oxygenase-1 and cyclo-oxygenase-2 in the ductus arteriosus from foetal lamb: differential development and change by oxygen and endotoxin. In: British Journal of Pharmacology, vol. 132 (01) pp. 241 - 251. British Pharmalogical Society, 2001.
Prenatal patency of the ductus arteriosus is maintained mainly by prostaglandin(PG) E2. Here we have examined the relative importance of cyclo-oxygenase-1 (COX1) and cyclo-oxygenase-2 (COX2) for PGE2 formation in the foetal lamb ductus (0.65 gestation onwards). 2 Using ¯uorescence microscopy and immunogold staining, COX1 appeared more abundant than COX2 in endothelial and smooth muscle cells, and this di€erence was greater before-term. Inside muscle cells, COX1 and COX2 immunoreactivity was located primarily in the perinuclear region. Endotoxin, given to the lamb in utero (*0.1 mg kg71), caused COX2 upregulation, while an opposite e€ect with disappearance of the enzyme followed endotoxin treatment in vitro (100 ng ml71). COX1 immunoreactivity remained virtually unchanged with either treatment; however, this isoform as well as any induced COX2 migrated towards the outer cytoplasm. 3 The COX2 inhibitor L-745,337 (1 ± 10 mM) contracted the isolated ductus at term, the response being almost as high as that to indomethacin (dual COX1/COX2 inhibitor) over the same dose- range. Conversely, L-745,337 was relatively less e€ective in the premature. 4 Pretreatment of the premature in vivo with endotoxin enhanced the contraction of the ductus to L-745,337, while in vitro endotoxin had a variable e€ect. 5 The premature ductus exhibited a stronger contraction to L-745,337 following exposure to oxygen. On the other hand, the oxygen contraction, which is modest before-term, was enhanced by L-745,337. 6 We conclude that COX1 and COX2 develop unevenly in the ductus. While both enzymes contribute to PGE2 formation at term, COX1 is the major isoform in the premature. COX2, however, may acquire greater importance before-term following physiological and pathophysiological stimuli.
URL: http://www.nature.com/bjp/journal/v132/n1/pdf/0703779a.pdf
Subject Ductus arteriosus
prostaglandin E2
foetal development

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