Cyclooxygenase isoforms and prostaglandin E2 receptors in the ductus arteriosus
2002; Elsevier BV; Volume: 63; Issue: 10 Linguagem: Inglês
10.1016/s0011-393x(02)80072-8
ISSN1879-0313
AutoresAsmàa Bouayad, Xin Hou, Daya R. Varma, Ronald I. Clyman, Jean‐Claude Fouron, Sylvain Chemtob,
Tópico(s)Peptidase Inhibition and Analysis
ResumoBackground: A patent ductus arteriosus (DA) promotes fetal development. However, the DA must close immediately after birth. Prostaglandin E2 (PGE2) is the most important factor in the regulation of DA tone during fetal development. This eicosanoid is generated through the activities of cyclooxygenases-1 (COX-1) and -2 (COX-2) and mediates its effects by interacting with G protein-coupled E-prostanoid (EP) receptors EP1, EP2, EP3, and EP4. Objective: This article summarizes the role of COX-1 and -2 and PGE2 receptors in fetal and neonatal DA tone. Methods: A MEDLINE search was performed of the English-language literature, using the terms ductus arteriosus, PGE2, and lamb. Results: The DA is less responsive to PGE2 in neonates than in fetuses. EP receptor subtypes 2 to 4 are expressed equivalently in fetal DA. Stimulation of all 3 receptor subtypes relaxes the DA. In the DA of newborns delivered at full term, EP2 remains unchanged, EP4 decreases, and changes in EP3 expression are equivocal. The DA is less responsive to PGE2 in newborns than in fetuses. The EP4 receptor may represent a possible therapeutic target for regulating DA tone in premature newborns. An EP2 agonist might be useful for maintaining DA patency in neonates and children with certain congenital heart diseases. Conclusions: COX-1 is the predominant isoenzyme in fetal DA, whereas COX-2 is upregulated in the DA immediately following birth. More research on patent DA and the role of preterm labor versus cesarean delivery is needed, as well as comparisons of the efficacy of selective EP-receptor targeting and enzymatic inhibition of COX and PGE2 synthetases.
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