Human big-endothelin-1 and endothelin-1 release prostacyclin via the activation of ET1 receptors in the rat perfused lung.
Although ET1 and ET2 binding sites were found in rat lung membranes, a selective ET1 receptor antagonist, BQ-123 (10 microM), did not displace [125I]-endothelin-1 ([125I]ET-1) from ET2 sites, illustrating the selectivity of the angatonist for ET1 receptors. In rat perfused lungs, BQ-123 (1 microM) markedly reduced the prostacyclin (PGI2) releasing properties of endothelin-1 (ET-1: 5 nM) and human big-ET-1 (100 nM) suggesting that both peptides induce the release of PGI2 via the selective activation of ET1 receptors.
D'Orléans-Juste
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P
Department of Pharmacology, Medical School, Université de Sherbrooke, Québec, Canada.
Télémaque
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S
Claing
A
A
Ihara
M
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Yano
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D000818:Animals; D019332:Endothelin-1; D016232:Endothelins / Q000494:pharmacology*; D011464:Epoprostenol / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology; D017466:Receptors, Endothelin
D019332:Endothelin-1; D016232:Endothelins; D010456:Peptides, Cyclic; D011498:Protein Precursors; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D011464:Epoprostenol; C072247:cyclo(Trp-Asp-Pro-Val-Leu)