Conversion of Big Endothelin-1 and Characterization of Its Contractile Effects on Isolated Human Placental Arteries
Objectives: To study the conversion of human big endothelin-1 (bigET-1) to endothelin-1 (ET-1) and to characterize contractile ET-1 receptors in human placental arteries. Methods: BigET-1 was incubated with artery membranes and the formation of ET-1 was investigated. ET-1 and bigET-1-induced contrac...
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Published in | Gynecologic and obstetric investigation Vol. 45; no. 1; pp. 1 - 6 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Basel, Switzerland
Karger
01.01.1998
S. Karger AG |
Subjects | |
Online Access | Get full text |
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Summary: | Objectives: To study the conversion of human big endothelin-1 (bigET-1) to endothelin-1 (ET-1) and to characterize contractile ET-1 receptors in human placental arteries. Methods: BigET-1 was incubated with artery membranes and the formation of ET-1 was investigated. ET-1 and bigET-1-induced contractile responses were studied in the absence or presence of the metalloprotease inhibitor phosphoramidon, the ET A -receptor antagonist BQ 123, or the ET B -receptor antagonists IRL 1038 and RES 701-1. Results: The artery membranes hydrolysed bigET-1 to ET-1 through a partly phosphoramidon-sensitive pathway. The contractile responses to ET-1 and bigET-1 were similar, with pEC 50% values of 8.1 ± 0.2 and 7.8 ± 0.1, respectively (NS; n = 17). Phosphoramidon decreased pEC 50% for bigET-1-evoked contractions (p < 0.05; n = 8), without affecting the response to ET-1. A Schild plot of BQ 123 effects on ET-1 and bigET-1-induced contractions resulted in identical pA 2 values and a slope of 0.56 ± 0.2 and 0.47 ± 0.01, respectively. IRL 1038 and RES 701-1 did not affect the contractile responses. Conclusion: BigET-1-evoked contractions in isolated human placental arteries depend on a rapid and metalloprotease-dependent hydrolytic conversion to ET-1, which in turn causes a, mainly ET A -receptor-mediated, contraction. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0378-7346 1423-002X |
DOI: | 10.1159/000009913 |