title: Endothelin-induced phosphoinositide hydrolysis in the muscular layer of stem villi vessels of human term placenta.
abstract: In the present study, we examined the relationship between endothelin receptors and phosphoinositide breakdown in muscle explants of placental stem villi vessels. All peptides examined, i.e. endothelin-1 (ET-1), ET-3, sarafotoxin 6b (S6b) and S6c, were able to induce phosphoinositide hydrolysis in a dose-dependent manner: ET-1 was more potent than S6b and ET-3, with corresponding EC50 values of 44 +/- 16 pmol/l, 18 +/- 13 nmol/l and 33 +/- 24 nmol/l, respectively. Sarafotoxin induced only moderate stimulation of inositol phosphate accumulation. Both ET-1- and S6b-induced accumulation of inositol phosphate was almost totally (90%) inhibited by 100 mumol/l BQ 123, while the S6c response was not affected by the ETA receptor antagonist. In contrast, the ETB receptor antagonist IRL 1038 inhibited S6c-induced inositol phosphate accumulation by more than 80%, whereas inhibition was only about 30% for ET-1 and S6b stimulations. This indicates that both ETA and ETB receptors were coupled to the phospholipase C transducing system in the muscular layer of placental stem villi vessels, and there is evidence that the phosphoinositide hydrolysis response is obtained predominantly via ETA receptor activation.
authors.affiliation: INSERM U.361, Université René Descartes, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Mondon
authors.forename: F
authors.initials: F
authors.lastname: Doualla-Bell Kotto Maka
authors.forename: S
authors.initials: S
authors.lastname: Sabry
authors.forename: F
authors.initials: F
authors.lastname: Ferré
mesh_terms: D000595:Amino Acid Sequence; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006868:Hydrolysis; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D010920:Placenta / Q000098:blood supply*; D011247:Pregnancy; D017466:Receptors, Endothelin / Q000819:agonists / Q000032:analysis; D010738:Type C Phospholipases / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
chemical_list: D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D009842:Oligopeptides; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D010716:Phosphatidylinositols; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; C087220:BQ 610; C077420:Cys(11)-Cys(15)-endothelin-1 (11-21); D010738:Type C Phospholipases; C072247:cyclo(Trp-Asp-Pro-Val-Leu)